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Study Design: Randomized controlled trial with 1-year follow up., Objective: The aim of this study was to assess whether people with low back pain (LBP) and self-reported physically demanding jobs, benefit from an occupational medicine intervention, in addition to a single hospital consultation and a magnetic resonance imaging, at 1 year of follow-up. Secondly, to examine whether the positive health effects, found in both groups at 6 months, persist at 1-year follow-up., Summary of Background Data: The prevalence of LBP is high in the working population, resulting in a substantial social and economic burden. Although there are many guidelines available on the management of LBP, including multidisciplinary biopsychosocial rehabilitation, they provide limited guidance on the occupational medicine aspects., Methods: As reported previously, 305 participants with LBP and self-reported physically demanding jobs were enrolled in the randomized controlled study and randomly allocated to clinical care with additional occupational medicine intervention or clinical care alone. Data were collected at baseline, 6 months, and 1 year. Outcomes included in the present 1-year follow-up study are changes in neuropathic pain (painDETECT questionnaire), severity of pain (0-10 numerical rating scale), disability (Roland Morris Disability Questionnaire), fear-avoidance beliefs (FABQ), physical, and mental quality of life (short-form 36)., Results: The study showed no effect of an occupational intervention on neuropathic pain, fear-avoidance beliefs, physical and mental quality of life nor disability measured after 1 year. The positive effects found at 6 months in both groups, remained at 1-year follow-up., Conclusion: The results suggest that a thorough clinical consultation, with focus on explaining the cause of pain and instructions to stay active, can promote long-lasting physical and mental health in individuals with LBP. Therefore, additional occupational interventions could focus on altering occupational obstacles on a structural level.Level of Evidence: 2., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Intergenerational effects are described as the genetic, epigenetic, as well as pre- and postnatal environmental influence parents have on their offspring's behavior, cognition, and brain. During fetal brain development, the primary cortical sulci emerge with a distinctive folding pattern that are under strong genetic influence and show little change of this pattern throughout postnatal brain development. We examined intergenerational transmission of cortical sulcal patterns by comparing primary sulcal patterns between children (N = 16, age 5.5 ± 0.81 years, 8 males) and their biological mothers (N = 15, age 39.72 ± 4.68 years) as well as between children and unrelated adult females. Our graph-based sulcal pattern comparison method detected stronger sulcal pattern similarity for child-mother pairs than child-unrelated pairs, where higher similarity between child-mother pairs was observed mostly for the right lobar regions. Our results also show that child-mother versus child-unrelated pairs differ for daughters and sons with a trend toward significance, particularly for the left hemisphere lobar regions. This is the first study to reveal significant intergenerational transmission of cortical sulcal patterns, and our results have important implications for the study of the heritability of complex behaviors, brain-based disorders, the identification of biomarkers, and targets for interventions., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

It has been suggested that specific forms of cognition in older age rely largely on late-life specific mechanisms. Here instead, we tested using task-fMRI (n = 540, age 6-82 years) whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural, and evolutionary influences. We clustered regions of the cerebral cortex according to the shape of the lifespan trajectory of memory activity in each region so that regions showing the same pattern were clustered together. The results revealed that lifespan trajectories of memory encoding function showed a continuity through life but no evidence of age-specific mechanisms such as compensatory patterns. Encoding activity was related to general cognitive abilities and variations of grey matter as captured by a multi-modal independent component analysis, variables reflecting core aspects of cognitive and structural change throughout the lifespan. Furthermore, memory encoding activity aligned to fundamental aspects of brain organization, such as large-scale connectivity and evolutionary cortical expansion gradients. Altogether, we provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only., (© The Author(s) 2020. Published by Oxford University Press.)

A complete picture of how subcortical nodes, such as the thalamus, exert directional influence on large-scale brain network interactions across age remains elusive. Using directed functional connectivity and weighted net causal outflow on resting-state fMRI data, we provide evidence of a comprehensive reorganization within and between neurocognitive networks (default mode: DMN, salience: SN, and central executive: CEN) associated with age and thalamocortical interactions. We hypothesize that thalamus subserves both modality-specific and integrative hub role in organizing causal weighted outflow among large-scale neurocognitive networks. To this end, we observe that within-network directed functional connectivity is driven by thalamus and progressively weakens with age. Secondly, we find that age-associated increase in between CEN- and DMN-directed functional connectivity is driven by both the SN and the thalamus. Furthermore, left and right thalami act as a causal integrative hub exhibiting substantial interactions with neurocognitive networks with aging and play a crucial role in reconfiguring network outflow. Notably, these results were largely replicated on an independent dataset of matched young and old individuals. Our findings strengthen the hypothesis that the thalamus is a key causal hub balancing both within- and between-network connectivity associated with age and maintenance of cognitive functioning with aging., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000-3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Importance: Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain., Objective: To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH., Data Sources: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline-compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome., Study Selection: Original studies in English language reporting 10 or more patients with SIH were selected by consensus., Data Extraction and Synthesis: Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Random-effect meta-analyses were used to calculate pooled estimates of means and proportions., Main Outcomes and Measures: The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical)., Results: Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%-96%]), nausea (54% [95% CI, 46%-62%]), and neck pain/stiffness (43% [95% CI, 32%-53%]). Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%-80%) of patients. Brain magnetic resonance imaging findings were normal in 19% (95% CI, 13%-24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60-200 mm H2O), and high in 67% (95% CI, 54%-80%), 32% (95% CI, 20%-44%), and 3% (95% CI, 1%-6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%-37%) of patients and a single epidural blood patch was successful in 64% (95% CI, 56%-72%). Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%-91%] and 66% [95% CI, 55%-77%], respectively)., Conclusions and Relevance: Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research.

OBJECTIVE. The purpose of this article is to review currently available and emerging techniques for pediatric lung MRI for general radiologists. CONCLUSION. MRI is a radiation-free alternative to CT, and clearly understanding the strengths and limitations of established and emerging techniques of pediatric lung MRI can allow practitioners to select and combine the optimal techniques, apply them in clinical practice, and potentially improve early diagnostic accuracy and patient management.

Study Design: Retrospective study (data analysis)., Objective: The purpose of this study was to assess the role of different factors on postoperative outcome of patients with degenerative cervical myelopathy (DCM)., Summary of Background Data: Ongoing degenerative changes of DCM lead to progressive neurological deficits. The optimal timing of surgical treatment is still unclear, especially in patients with mild DCM., Methods: Patients with DCM treated in our clinic between 2007 and 2016 were retrospectively analyzed. Pre- and postoperative neurological function was assessed by the modified Japanese Orthopaedic Association Score (mJOA Score) at different stages. The minimum clinically important difference (MCID) was used to evaluate the improvement after surgery. The comorbidities were recorded using the Charlson Comorbidity Index (CCI). Possible associations between age, sex, CCI, preoperative symptoms duration, high signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) with mJOA Score and MCID were analyzed using univariate analysis and multivariate regression models. Additionally, subgroup analysis was performed according to the severity of DCM (mild: mJOA Score ≥15 points; moderate: mJOA Score of 12-14 points; and severe: mJOA Score <12 points)., Results: The mean age of the final cohort (n = 411) was 62.6 years (range: 31-96 years), 36.0% were females. High SI on T2-weighted MRI was detected in 60.3% of the cases. In the multivariate analysis, patients' age (P = 0.005), higher CCI (P = 0.001), and presence of high SI on T2-weighted MRI (P = 0.0005) were associated independently with lower pre- and postoperative mJOA Score and postoperative MCID. Subgroup analysis revealed age and high SI on T2-weighted MRI as predictors of pre- and postoperative mJOA. However, symptom duration did not influence neurological outcome according to the severity of DCM., Conclusion: Surgery for DCM leads to significant functional improvement. However, better outcome was observed in younger individuals with lower CCI and absence of radiographic myelopathy signs. Therefore, DCM surgery, particularly before occurrence of high SI on MRI, seems to be essential for postoperative functional improvement regardless the above-mentioned confounders.Level of Evidence: 3., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS., Observations: Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS. In patients with PPMS and those with relapse-onset MS, location of lesions in critical central nervous system regions (spinal cord, infratentorial regions, and GM) and MRI-detected high inflammatory activity in the first years after diagnosis are risk factors for long-term disability and future progressive disease course. These measures are evaluable in clinical practice. In patients with established MS, GM involvement and neurodegeneration are associated with accelerated clinical worsening. Subpial demyelination and slowly expanding lesions are novel indicators of progressive MS., Conclusions and Relevance: Diagnosis of PPMS is more challenging than diagnosis of RRMS. No qualitative clinical, immunological, histopathological, or neuroimaging features differentiate PPMS and SPMS; both are characterized by imaging findings reflecting neurodegeneration and are also impacted by aging and comorbidities. Unmet diagnostic needs include identification of MRI markers capable of distinguishing PPMS from RRMS and predicting the evolution of RRMS to SPMS. Integration of multiple parameters will likely be essential to achieve these aims.

Background: Decline in neurocognitive functioning (NCF) often occurs following brain tumor resection. Functional connectomics have shown how neurologic insults disrupt cerebral networks underlying NCF, though studies involving patients with brain tumors are lacking., Objective: To investigate the impact of brain tumor resection upon the connectome and relationships with NCF outcome in the early postoperative period., Methods: A total of 15 right-handed adults with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessment before and after awake tumor resection. Graph theoretical analysis was applied to rs-fMRI connectivity matrices to calculate network properties. Network properties and NCF measures were compared across the pre- to postoperative periods with matched pairs Wilcoxon signed-rank tests. Associations between pre- to postoperative change in network and NCF measures were determined with Spearman rank-order correlations (ρ)., Results: A majority of the sample showed postoperative decline on 1 or more NCF measures. Significant postoperative NCF decline was found across measures of verbal memory, processing speed, executive functioning, receptive language, and a composite index. Regarding connectomic properties, betweenness centrality and assortativity were significantly smaller postoperatively, and reductions in these measures were associated with better NCF outcomes. Significant inverse associations (ρ = -.51 to -.78, all P < .05) were observed between change in language, executive functioning, and learning and memory, and alterations in segregation, centrality, and resilience network properties., Conclusion: Decline in NCF was common shortly following resection of glioma involving eloquent brain regions, most frequently in verbal learning/memory and executive functioning. Better postoperative outcomes accompanied reductions in centrality and resilience connectomic measures., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: To determine whether MS disease-modifying therapies (DMTs) can be safely discontinued in patients aged 50 years or older with suspected benign/burnt-out MS and to define criteria to identify such patients., Methods: We conducted a retrospective cohort study of 136 patients with suspected benign/burnt-out MS who discontinued DMTs from the electronic health record (EHR) at Kaiser Permanente Southern California., Results: The majority discontinued an injectable DMT (n = 131, 96%). At the time of DMT discontinuation, mean and SD for age was 60.6 (6.2) years, disease duration 19.5 (10.7) years, and time since last relapse 11.0 (7.2) years. After a mean duration of follow-up of 5.0 years post-DMT discontinuation, 5 (3.7%) patients had a relapse, 2 (1.5%) had mild residual deficits, and 3 (2.2%) had asymptomatic MRI disease activity. Patients with MS disease activity following DMT discontinuation were younger (median = 53.6 years) than those who remained disease activity free. Fifty patients (36.8%) had only 1 lifetime relapse, of whom 1 relapsed post-DMT discontinuation. Sixty (56.6%) of 106 patients with spinal cord MRIs before discontinuation showed demyelinating lesions., Conclusions: DMT discontinuation in older patients with suspected benign/burnt-out MS appears safe. Our findings suggest that MRI evidence of spinal cord involvement does not preclude the possibility of benign/burnt-out MS, and for those with 2 or more lifetime relapses, a benign/burn-out classification is best reserved for those aged 55 years and older. Future studies to determine whether DMT discontinuation is safe at a younger age in patients with a single lifetime relapse are needed., Classification of Evidence: The study provides Class IV evidence that DMTs can be safely discontinued in older patients with suspected benign/burnt-out MS., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence. SIGNIFICANCE STATEMENT An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development., (Copyright © 2021 Salvan et al.)

Brain lesions caused by cerebral ischemia or hemorrhage lead to a local breakdown of energy homeostasis followed by irreversible cell death and long-term impairment. Importantly, local brain lesions also generate remote functional and structural disturbances, which contribute to the behavioral deficit but also impact the recovery of function. While spontaneous recovery has been associated with endogenous repair mechanisms at the vascular, neural, and immune cell levels, the impact of structural plasticity on sensory-motor dysfunction and recovery thereof remains to be elucidated by longitudinal imaging in a mouse model. Here, we applied behavioral assessments, in vivo fiber tracking, and histological validation in a photothrombotic stroke mouse model. Atlas-based whole-brain structural connectivity analysis and ex vivo histology revealed secondary neurodegeneration in the ipsilesional brain areas, mostly in the dorsal sensorimotor area of the thalamus. Furthermore, we describe for the first time a lesion size-dependent increase in structural connectivity between the contralesional primary motor cortex and thalamus with the ipsilesional cortex. The involvement of the contralesional hemisphere was associated with improved functional recovery relative to lesion size. This study highlights the importance of in vivo fiber tracking and the role of the contralesional hemisphere during spontaneous functional improvement as a potential novel stroke biomarker and therapeutic targets.

Background: Low back pain (LBP) is increasing in the pediatric population. Advanced imaging, such as computed tomography and magnetic resonance imaging, performed for LBP imposes significant costs with little benefit. We investigated annual trends and demographic and geographic variation in spinal imaging for first-time pediatric presenters with LBP in primary care clinics., Methods: We queried a private administrative claims database for patients presenting with LBP who underwent plain radiography, computed tomography, and magnetic resonance imaging from 2011 to 2017. We used a Cochrane Armitage test of trend to determine significant annual variation in diagnostic imaging utilization during the study period. The χ 2 test was used to determine demographic and geographic variation., Results: The study included 67,423 patients with mean age 15.2 ± 3 years. There was no significant change in radiography (34.8% in 2011 vs. 35.5% in 2017, P = 0.795) or computed tomography (1.6% in 2011 vs. 1.1% in 2017, P = 0.073), but there was a significant increase in magnetic resonance imaging (3.3% in 2011 vs. 4.5% in 2017, P = 0.017). Overall, there was no significant change in total imaging use (P = 0.895). Boys had higher rates of imaging compared with girls (40.2% vs. 35.6%, P < 0.001). Imaging rates significantly varied between regions across the United States (P < 0.001). The Midwest had the highest imaging rates (41%), while the Northeast had the lowest rates (31%)., Conclusions: There was significant demographic and geographic variation but no significant annual change in total diagnostic spinal imaging for pediatric patients with LBP between 2011 and 2017, with rates of advanced imaging remaining relatively low., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To establish progression of imaging biomarkers of stroke, arterial steno-occlusive disease, and white matter injury in patients with smooth muscle dysfunction syndrome caused by mutations in the ACTA2 gene, we analyzed 113 cerebral MRI scans from a retrospective cohort of 27 patients with ACTA2 Arg179 pathogenic variants., Methods: Systematic quantifications of arterial ischemic strokes and white matter lesions were performed on baseline and follow-up scans using planimetric methods. Critical stenosis and arterial vessel diameters were quantified applying manual and semiautomated methods to cerebral magnetic resonance angiograms. We then assessed correlations between arterial abnormalities and parenchymal injury., Results: We found characteristic patterns of acute white matter ischemic injury and progressive internal carotid artery stenosis during infancy. Longitudinal analysis of patients older than 1.2 years showed stable white matter hyperintensities but increased number of cystic-like lesions over time. Progressive narrowing of the terminal internal carotid artery occurred in 80% of patients and correlated with the number of critical stenoses in cerebral arteries and arterial ischemic infarctions. Arterial ischemic strokes occurred in same territories affected by critical stenosis., Conclusions: We found characteristic, early, and progressive cerebrovascular abnormalities in patients with ACTA2 Arg179 pathogenic variants. Our longitudinal data suggest that while steno-occlusive disease progresses over time and is associated with arterial ischemic infarctions and cystic-like white matter lesions, white matter hyperintensities can remain stable over long periods. The evaluated metrics will enable diagnosis in early infancy and be used to monitor disease progression, guide timing of stroke preventive interventions, and assess response to current and future therapies., (© 2020 American Academy of Neurology.)

Objective: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS)., Methods: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired patients with MS aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle., Results: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% confidence interval [CI] -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O 2 /min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group., Conclusion: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted., Clinicaltrialsgov Identifier: NCT02661555., Classification of Evidence: This study provides Level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate., (© 2020 American Academy of Neurology.)

Children and adolescents show high variability in brain development. Brain age-the estimated biological age of an individual brain-can be used to index developmental stage. In a longitudinal sample of adolescents (age 9-23 years), including monozygotic and dizygotic twins and their siblings, structural magnetic resonance imaging scans (N = 673) at 3 time points were acquired. Using brain morphology data of different types and at different spatial scales, brain age predictors were trained and validated. Differences in brain age between males and females were assessed and the heritability of individual variation in brain age gaps was calculated. On average, females were ahead of males by at most 1 year, but similar aging patterns were found for both sexes. The difference between brain age and chronological age was heritable, as was the change in brain age gap over time. In conclusion, females and males show similar developmental ("aging") patterns but, on average, females pass through this development earlier. Reliable brain age predictors may be used to detect (extreme) deviations in developmental state of the brain early, possibly indicating aberrant development as a sign of risk of neurodevelopmental disorders., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The myeloarchitecture of the corpus callosum (CC) is characterized as a mosaic of distinct differences in fiber density of small- and large-diameter axons along the anterior-posterior axis; however, regional and age differences across the lifespan are not fully understood. Using multiecho T2 magnetic resonance imaging combined with multi-T2 fitting, the myelin water fraction (MWF) and geometric-mean of the intra-/extracellular water T2 (geomT2IEW) in 395 individuals (7-85 years; 41% males) were examined. The approach was validated where regional patterns along the CC closely resembled the histology; MWF matched mean axon diameter and geomT2IEW mirrored the density of large-caliber axons. Across the lifespan, MWF exhibited a quadratic association with age in all 10 CC regions with evidence of a positive linear MWF-age relationship among younger participants and minimal age differences in the remainder of the lifespan. Regarding geomT2IEW, a significant linear age × region interaction reflected positive linear age dependence mostly prominent in the regions with the highest density of small-caliber fibers-genu and splenium. In all, these two indicators characterize distinct attributes that are consistent with histology, which is a first. In addition, these results conform to rapid developmental progression of CC myelination leveling in middle age as well as age-related degradation of axon sheaths in older adults., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Brain development and aging are complex processes that unfold in multiple brain regions simultaneously. Recently, models of brain age prediction have aroused great interest, as these models can potentially help to understand neurological diseases and elucidate basic neurobiological mechanisms. We test whether quantitative magnetic resonance imaging can contribute to such age prediction models. Using R1, the longitudinal rate of relaxation, we explore lifespan dynamics in cortical gray matter. We compare R1 with cortical thickness, a well-established biomarker of brain development and aging. Using 160 healthy individuals (6-81 years old), we found that R1 and cortical thickness predicted age similarly, but the regions contributing to the prediction differed. Next, we characterized R1 development and aging dynamics. Compared with anterior regions, in posterior regions we found an earlier R1 peak but a steeper postpeak decline. We replicate these findings: firstly, we tested a subset (N = 10) of the original dataset for whom we had additional scans at a lower resolution; and second, we verified the results on an independent dataset (N = 34). Finally, we compared the age prediction models on a subset of 10 patients with multiple sclerosis. The patients are predicted older than their chronological age using R1 but not with cortical thickness., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Breast magnetic resonance (MR) imaging is the most sensitive imaging modality for breast cancer detection and guidelines recommend its use, in addition to screening mammography, for high-risk women. The most recent American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) manual coordinated cross-modality BI-RADS terminology and established an outcome monitoring section that helps guide a medical imaging outcomes audit. This article provides a framework for performing a breast MR imaging audit in clinical practice, incorporating ACR BI-RADS guidance and more recently published data, clarifies common pitfalls, and discusses audit challenges related to evolving clinical practice., Competing Interests: Disclosure Dr J.M. Lee has a research grant from GE Healthcare, United States., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Recent cross-sectional studies highlighted the loss of dopaminergic neurons in the ventral tegmental area (VTA) as an early pathophysiological event in Alzheimer's disease (AD)., Objective: In this study, we longitudinally investigated by resting-state fMRI (rs-fMRI) a cohort of patients with mild cognitive impairment (MCI) due to AD to evaluate the impact of VTA disconnection in predicting the conversion to AD., Methods: A cohort of 35 patients with MCI due to AD were recruited and followed-up for 24 months. They underwent cognitive evaluation and rs-fMRI to assess VTA connectivity at baseline and at follow-up., Results: At 24-month follow-up, 16 out of 35 patients converted to AD. Although converters and non-converters to AD did not differ in demographic and behavioral characteristics at baseline, the first group showed a significant reduction of VTA-driven connectivity in the posterior cingulate and precentral cortex. This pattern of additional disconnection in MCI-Converters compared to non-converters remained substantially unchanged at 24-month follow-up., Conclusion: This study reinforces the hypothesis of an early contribution of dopaminergic dysfunction to AD evolution by targeting the default-mode network. These results have potential implications for AD staging and prognosis and support new opportunities for therapeutic interventions to slow down disease progression.

Objective: The aim of this study was to determine common structural and functional networks associated with asymmetric step length after unilateral ischemic stroke., Methods: Thirty-nine chronic stroke patients were divided into two groups, based on the presence or absence of asymmetric step length. In each group, each lesion was mapped onto a brain magnetic resonance image. The structural and functional networks of brain regions connected to each lesion were identified using a public diffusion tensor and resting state function magnetic resonance image dataset. To identify brain regions associated with asymmetric step length, we conducted voxel-wise independent sample t-tests for structural and function lesion network maps., Results: At least 85% of lesions showed functional network overlap in the bilateral frontal lobe. Functional connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere was significantly decreased in group 1 compared to that in group 2., Conclusions: The dorsolateral prefrontal cortex may have an important role in compensating for an asymmetric step length after a unilateral stroke.

Aim: To reveal the correlation between total cerebrovascular disease load and primary lacunar infarction., Background: Cerebral small vessel disease (CSVD) is the lack of specific clinical manifestations, whose clinical diagnoses are highly dependent on neuroimaging results. Total CSVD load scores may be more suitable for the assessment of overall brain function damage caused by CSVD. Little is known about whether the association between imaging markers of CSVD and CSVD total load scores at the time of first-ever lacunar infarction (LI)., Methods: clinical data of 396 patients hospitalised from September 2016 to May 2018 due to a first-ever LI (case group), along with patients diagnosed with CSVD based on imaging alone and those with no abnormalities (control group) based on magnetic resonance imaging (MRI). Binary logistic regression and multiple ordered logistic regression were used to analyse the characteristics of imaging markers of CSVD in patients with first-ever LI, including different total score burden and distribution, and the relationship between different markers., Results: In 396 patients, smoking, cholesterol level and total small vessel disease (SVD) score were all significantly associated with the first-ever LI. There were more LI, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and moderate to severe enlarged perivascular spaces (EPVS) in the first-ever LI group, relative to controls (p < 0.01). The Fazekas scores for periventricular WMH, deep WMH, and total Fazekas score were all significantly higher in patients with first-ever LI relative to those with no cerebral abnormalities (p < 0.01). An analysis of various imaging markers of CSVD revealed a significant correlation between the presence and degree of any marker and the severity of other markers, even after adjusting for the presence of other markers (p < 0.05)., Conclusions: The first-ever LI group exhibited higher total CSVD score loads, a greater number of lacunae, CMB, severe WMH and moderate to severe EPVS. Smoking is an independent risk factor in patients with first-ever LI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease caused a challenging and threating pandemic (COVID-19) worldwide with a great loss to life and the global economy. SARS-CoV-2 mainly involves the respiratory system, however, with Magnetic Resonance Imaging (MRI), neurological and special senses clinical manifestations have been reported rarely. The present study aims to investigate the MRI findings, clinical manifestations of neurological and special senses involvement in SARS-CoV-2 patients., Materials and Methods: In this study, 284 articles from the databases "Pub-Med, Web of Science-Clarivate Analytics, Embase and Google Scholar" were identified. The keywords, coronavirus, SARS-CoV-2, COVID-19 pandemic, MRI, brain, special senses, neurological involvement were entered into the search engines and the concerned documents were selected and reviewed. The descriptive information was recorded from the particular studies; finally, we included 48 publications., Results: The common neurological manifestations in SARS-CoV-2 patients were headache, impaired consciousness, acute cerebrovascular disease, ataxia, tremors, meningitis, encephalitis, cerebral bleeding, subarachnoid hemorrhage, frontal lobe, temporal lobe and intracerebral hematoma, hemiparesis and seizures. However, common special senses manifestations in SARS-CoV-2 patients were olfactory, auditory and gustatory disorders including red eyes, painless monocular visual disturbance, anosmia, ageusia, dysgeusia, dysosmia and hypoacusis. Moreover, the MRI findings identified in SARS-CoV-2 patients were isolated oval-shaped lesion in the corpus callosum, bilateral basal ganglia hemorrhage, ischemic lesions involving the corpus callosum, basal ganglia, cerebellum and vasogenic edema extending to the cerebral peduncles, pons and ventricles., Conclusions: The neurologic manifestations of SARS-CoV-2 patients are highly variable. The SARS-COV-2 exerts its damaging effects on the nervous system and special senses by developing determinant numerous neurological and special senses' clinical manifestations. Physicians with the help of MRI must rule out the neurological and special senses manifestations among SARS-CoV-2 patients.

Background: APOEɛ4 allele carriers present with an increased risk for late-onset Alzheimer's disease (AD), show cognitive symptoms at an earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ4 allele controls the rate of disease progression., Objective: To determine the effects of the ɛ4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD., Methods: A segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain volumetric data of 73 ɛ3/ɛ3, 99 ɛ3/ɛ4, and 39 ɛ4/ɛ4 Alzheimer's Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia., Results: ɛ4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ4 allele-dose effects after dementia transition but not during MCI. The ɛ4 effect was more prevalent in younger participants and in females. ɛ4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI., Conclusion: Possession of the ɛ4 allele is associated with a faster progression of dementia due to AD. Our observations support the notion that APOE genotype not only controls AD risk but also differentially regulates mechanisms of neurodegeneration underlying disease advancement. Furthermore, our findings carry significance for AD clinical trial design.

Magnetic resonance-guided focused ultrasound is a powerful new technology that is enabling development of noninvasive applications for complex brain disorders. This is currently revolutionizing the treatment of tremor disorders, and a variety of experimental applications are under active investigation. To fully realize the potential of this disruptive technology, many challenges have been identified, some of which have been addressed and others remain to be solved. As an image-based technology, optimal intraoperative imaging can be difficult to achieve and several factors can influence the quality of these images. Technical issues with current devices can also limit the effective delivery of ultrasound technology to particular targets. While lesioning is the primary approved application of magnetic resonance-guided focused ultrasound at present, the ability to transient and precisely open the blood-brain barrier has the potential to clear brain pathologies and deliver restorative therapies, but this more experimental method presents unique difficulties to overcome. Finally, regulatory and reimbursement hurdles currently remain complex and continue to limit widespread application of even approved, effective applications. Here we review many of these challenges, discuss several solutions that have already been developed, and propose potential options for addressing some of these complexities in the future., (Copyright © 2020. Published by Elsevier Inc.)

Background: Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction., Objective: We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance)., Methods: 32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression., Results: There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants., Conclusion: Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a cutting-edge technology that is changing the practice of movement disorders surgery. Given the noninvasive and innovative nature of this technology, there is great interest in expanding the use of MRgFUS to additional diseases and applications. Current approved applications target the motor thalamus to treat tremor, but clinical trials are exploring or plan to study noninvasive lesions with MRgFUS to ablate tumor cells in the brain as well as novel targets for movement disorders and brain regions associated with pain and epilepsy. Although there are additional potential indications for lesioning, the ability to improve function by destroying parts of the brain is still limited. However, MRgFUS can also be applied to a brain target after intravenous delivery of microbubbles to create cavitations and focally open the blood-brain barrier (BBB). This has already proven to be safe and technically feasible in human patients with Alzheimer's disease, and this action alone has potential to clear extracellular pathology associated with this and other neurodegenerative disorders. This also provides a foundation for noninvasive intravenous delivery of therapeutic molecules to precise brain targets after transient disruption of the BBB. Certain chemotherapies for brain tumors, immunotherapies, gene, and cell therapies are all examples of therapeutic or even restorative agents that normally will not enter the brain without direct infusion but which have been shown in preclinical studies to effectively traverse the BBB after transient disruption with MRgFUS. Here we will review these novel applications of MRgFUS to provide an overview of the extraordinary potential of this technology to expand future neurosurgical treatments of brain diseases., (Copyright © 2020. Published by Elsevier Inc.)

Background: Magnetic resonance imaging (MRI) of the prostate (MRI-prostate) facilitates better detection of clinically significant prostate cancer (PCa). Yet, the national trends of MRI at the time of prostate biopsy and its ability to increase the detection of PCa in a biopsy-naïve population remain unknown., Objective: To elucidate the contemporary trends of MRI and prostate biopsy, and whether it improved PCa diagnosis among privately insured patients., Design, Setting, and Participants: This was a retrospective cohort study of a large private health insurance database in the USA-the OptumLabs Data Warehouse. We identified all men ≥40 yr of age who underwent index prostate biopsies from 2010 through 2016., Intervention: MRI-prostate at the time of index biopsy., Outcome Measurements and Statistical Analysis: Utilization of the MRI at the time of biopsy and incident PCa diagnosis constituted the primary outcomes. We enumerated unadjusted and age-specific annual rates of MRI over time to elucidate trends using regression models (trend analysis). Bivariate and multivariable regression analyses identified patient characteristics associated with MRI-prostate, and the association between the use of MRI and PCa diagnosis., Results and Limitations: Overall, 119 202 men underwent index prostate biopsies. Unadjusted annual rates of MRI at the time of biopsy significantly increased from 7 per 1000 biopsies in 2010 to 83 per 1000 biopsies in 2016 (p < 0.001 for trend). Age-specific rates increased across all age groups (40-49, 50-59, 60-65, 66-74, and 75+ yr; all p < 0.001). On multivariable analysis, black patients had a lower likelihood of MRI compared with white patients (odds ratio [OR]: 0.6; p < 0.01). MRI at the time of biopsy was not associated with a higher likelihood of incident PCa compared with traditional systematic biopsy (OR: 1.0; p = 0.7). The retrospective design and the inability to detect clinically significant PCa (Gleason 7+) constitute the limitations of this study., Conclusions: While the use of MRI at the time of biopsy rose markedly, it was not associated with a higher detection rate of PCa. Further research is needed to address effective dissemination of MRI and targeted biopsies, and racial disparities., Patient Summary: From 2010 to 2016, our study found a significant rise in the utilization of magnetic resonance imaging of the prostate (MRI-prostate) at the time of index biopsy, although only a minority of patients undergo MRI-prostate. The use of MRI-prostate was not associated with a higher likelihood of diagnosing incident prostate cancer., (Copyright © 2019. Published by Elsevier B.V.)

Objective: The relationship between serum aryl hydrocarbon receptor (AHR) agonistic activity levels with disease severity, its modulation over the course of relapsing-remitting MS (RRMS), and its regulation in progressive MS (PMS) are unknown. Here, we report the analysis of AHR agonistic activity levels in cross-sectional and longitudinal serum samples of patients with RRMS and PMS., Methods: In a cross-sectional investigation, a total of 36 control patients diagnosed with noninflammatory diseases, 84 patients with RRMS, 35 patients with secondary progressive MS (SPMS), and 41 patients with primary progressive MS (PPMS) were included in this study. AHR activity was measured in a cell-based luciferase assay and correlated with age, sex, the presence of disease-modifying therapies, Expanded Disability Status Scale scores, and disease duration. In a second longitudinal investigation, we analyzed AHR activity in 13 patients diagnosed with RRMS over a period from 4 to 10 years and correlated AHR agonistic activity with white matter atrophy and lesion load volume changes., Results: In RRMS, AHR ligand levels were globally decreased and associated with disease duration and neurologic disability. In SPMS and PPMS, serum AHR agonistic activity was decreased and correlated with disease severity. Finally, in longitudinal serum samples of patients with RRMS, decreased AHR agonistic activity was linked to progressive CNS atrophy and increased lesion load., Conclusions: These findings suggest that serum AHR agonist levels negatively correlate with disability in RRMS and PMS and decrease longitudinally in correlation with MRI markers of disease progression. Thus, serum AHR agonistic activity may serve as novel biomarker for disability progression in MS., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Supplemental breast cancer screening with breast magnetic resonance imaging (MRI) is recommended for women at high risk of breast cancer. To the authors' knowledge, recent national trends in breast MRI use are unknown., Methods: The authors used claims data from a large national insurer to calculate screening breast MRI rates from 2006 to 2016 in a US cohort of 10 million women aged 20 to 64 years. Use was stratified by subgroups of women with a BRCA mutation, family history of breast cancer, and prior breast cancer history and stratified by age. Joinpoint regression evaluated annual changes in trends., Results: The total sample included 37,447 screening breast MRI examinations in 25,617 women. Overall screening breast MRI rates were low and increased from 2.9 to 12.1 examinations per 10,000 women from 2006 to 2016. MRI use in women with a BRCA mutation increased by 21% on average annually from 210.8 per 10,000 women to 1562.0 per 10,000 women from 2006 to 2016. By 2016, women aged 50 to 64 years who had a BRCA mutation had the highest use of breast MRI (1669.6 MRI examinations per 10,000 women) compared with younger women (1198.4 MRI examinations per 10,000 women, 1519.1 MRI examinations per 10,000 women, and 1567.2 MRI examinations per 10,000 women, respectively, among women aged 20-29 years, 30-39 years, and 40-49 years). Women with a BRCA mutation comprised <1% of the current study population but received approximately 9% of screening breast MRI examinations. Breast MRI rates among women with a family history of breast cancer or prior breast cancer history initially increased from 2006 to 2008, but then stabilized or decreased., Conclusions: The increases in breast MRI use observed in the current study have indicated improvements in concordance with breast imaging guidelines. However, women with BRCA mutations remain underscreened, particularly younger women, thereby identifying a clear gap with which to enhance access., (© 2020 American Cancer Society.)

Recent structural MRI studies on gray matter (GM) volumes using group-level mass-univariate statistical analysis suggest that chronic and heavy cannabis exposure may affect brain region-based morphology. In this prospective study, we use a multivariate pattern analysis approach to investigate the voxel-level change of GM densities in chronic heavy cannabis users. Principal component analysis and linear support vector machine are used in this study, resulting in an 88.1% separation between chronic heavy cannabis users (N = 20) and non-cannabis healthy controls (HCs, N = 22) through leave-one-out cross-validation. The model's discriminative pattern showed that GM density decreases in the part of middle frontal gyrus, inferior frontal gyrus, middle temporal gyrus, inferior temporal gyrus and left occipital lobe in heavy cannabis users with respect to HCs and increases in the part of lentiform nucleus, left cerebellum and right parietal lobe. These results suggest that GM densities alteration has taken place on chronic heavy cannabis users compared with HCs at voxel level.

Objective: There are concerns that lumbar spine imaging represents low value care. Our aim was to examine the use of lumbar spine imaging [radiography, computed tomography (CT), magnetic resonance imaging (MRI)] over 20 years, and costs and person-level characteristics of imaging in a large cohort of Australian women., Methods: The Australian Longitudinal Study on Women's Health (ALSWH) is a longitudinal population-based survey of women randomly selected from national health insurance scheme (Medicare) database. This study examined 13458 women born in 1973-1978 who consented to link their ALSWH and Medical Benefits Scheme records. Self-reported data on demographics, body mass index, depression, physical and mental health, and back pain were collected in each survey performed in 1996, 2000, 2003, 2006, 2009, 2012, and 2015. Data on lumbar spine imaging from 1996 to 2015 were obtained from the Medical Benefits Scheme database., Results: 38.9% of women underwent some form of lumbar spine imaging over 20 years. While radiography increased from 1996 to 2011 and decreased thereafter, CT and MRI continued to increase from 1996 to 2015. In women with self-reported back pain, depression and poorer physical health were associated with imaging, with no significant differences in types of imaging. Based on imaging rates in ALSWH, the estimated costs for Australian women aged 30-39 years were AU$51,735,649 over 2011-2015., Conclusions: Lumbar spine imaging was common in population-based Australian women, with rates increasing over 20 years. Depression and poor physical health were associated with lumbar spine imaging. Raising awareness of this in clinicians is likely to result in significant cost savings if clinical guidelines are followed, with the potential of freeing resources for high value care and health outcomes., Competing Interests: The authors have declared that no competing interests exist.

Patterns of change in whole-brain functional networks remain poorly understood in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). We conducted a prospective research to investigate the topological properties of whole-brain functional networks in those patients using a graph-based network analysis. Resting-state functional magnetic resonance imaging was performed on 51 ESRD patients (25 HD and 26 nondialysis patients) and 36 healthy controls (HCs). We compared the topological properties of brain functional networks among the three groups, and analyzed the relationships between those significant parameters and clinical variables in ESRD patients. Progressively disrupted global topological organizations were observed from nondialysis patients to HD patients compared with HCs (all p < 0.05 after Bonferroni correction). HD patients, relative to HCs, showed significantly decreased nodal centralities in the left temporal pole: superior temporal gyrus, bilateral median cingulate and paracingulate gyri, bilateral hippocampus, bilateral parahippocampal gyrus, and bilateral amygdala, and showed increased nodal centralities in the orbital part of the bilateral middle frontal gyrus, left cuneus, and left superior occipital gyrus (all p < 0.05 after Bonferroni correction). Furthermore, nodal centralities in the bilateral hippocampus were significantly decreased in HD patients compared with nondialysis patients (p < 0.05 after Bonferroni correction). Dialysis duration negatively correlated with global efficiency in ESRD patients undergoing HD (r = -0.676, FDR q = 0.004). This study indicates that ESRD patients exhibit disruptions in brain functional networks, which are more severe in HD patients, and these alterations are correlated with cognitive performance and clinical markers., (© 2020 Wiley Periodicals LLC.)

Background: Trials of endovascular thrombectomy (EVT) mostly excluded patients with large core strokes so the safety and efficacy of EVT is not well established in such patients. Moreover, the definition of large core and its measurement differ between semi-quantitative (ASPECTS) and quantitative (core volume) imaging modalities. We evaluated functional and safety outcomes in studies reporting large core stroke patients treated with EVT and compared them with patients treated with medical management (MM) only., Methods: A systemic search using three large databases was performed to identify studies evaluating functional and safety outcomes in patients with large core strokes (ASPECTS<6 or core volume ≥50 cc) on CT, MRI, and Perfusion imaging according to PRISMA guidelines. A random-effect meta-analysis model was used to pool reported outcomes., Results: Twelve studies reporting outcomes for patients treated with EVT compared with MM in large core strokes were included. A pooled random-effect meta-analysis of large core patients by either definition (ASPECTS <6 or ischemic core volume ≥50 cc or both) demonstrated increased functional independence (mRS-scores 0-2) rates with EVT (EVT: 122/491 (25%), MM: 45/691 (7%), pooled OR: 4.39 [95% CI: 2.53 to 7.64], overall effect Z-score: 5.25, P<0.00001, I 2 =37%, P for Cochran Q:0.15) and decreased mortality (EVT: 101/439 (23%), MM: 215/645 (33%), pooled OR:0.53 [95% CI: 0.40 to 0.71], overall effect Z-score:4.32, P<0.0001, I 2 =0%, P for Cochran Q:0.78) at 90 days, without significant increase in symptomatic intracranial hemorrhage (ICH) (EVT: 42/462 (9%), MM: 35/663 (5%), pooled OR: 1.68 [95% CI: 0.92 to 3.09], overall effect Z-score:1.68, P=0.09, I 2 =26%, P for Cochran Q:0.24). Similar effects were observed in studies reporting large core outcomes based on ASPECTS <6 and ischemic core volume ≥50 cc. We observed no heterogeneity between quantitative vs semi-quantitative large core definitions, different ischemic core thresholds, and studies reporting outcomes over different time windows in subgroup analyses., Conclusion: In large core stroke patients, EVT is associated with improved functional independence and lower mortality at 90 days without significant increase in symptomatic ICH across various definitions, thresholds of large core size, and time windows. Further randomized evidence is warranted to establish EVT efficacy and safety in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of this longitudinal study was to clarify whether significant alterations in structural connectivity occur over time in patients with newly diagnosed focal epilepsy of unknown origin., Methods: A total of 40 patients with newly diagnosed focal epilepsy of unknown origin and with normal brain magnetic resonance imaging (MRI) on visual inspection were enrolled. All subjects underwent MRI twice involving three-dimensional volumetric T1-weighted imaging, which were suitable for structural volume analysis. Gray matter volumes were obtained using the FreeSurfer image analysis suite, and structural connectivity analyses were performed using Matlab-based BRain Analysis using graPH theory software., Results: The median interval between the two MRI scans was 18.5 months in patients with epilepsy. There was a general tendency toward decreased gray matter volumes on the second scan compared with the initial scan. However, the volumes of the right and left thalamus and brainstem on the second MRI scan had an increased tendency compared with those on the initial MRI scan. In measures of connectivity, there were significant differences between the two MRI scans. The mean clustering coefficient, global efficiency, local efficiency, and the small-worldness index were significantly increased, whereas the characteristic path length was decreased on the second MRI scan compared with the initial MRI scan., Conclusions: The structural connectivity in patients with newly diagnosed focal epilepsy of unknown origin increases over time in the initial stage. These alterations and increases in structural connectivity may be related to underlying epileptogenicity in the initial stages of epilepsy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Rosai-Dorfman disease (RDD) is a rare pathologic entity caused by sinus histiocytosis with massive cervical lymphadenopathy. Isolated spinal involvement is an infrequent presentation of extranodal RDD. The clinical and radiologic appearance of RDD represents a diagnostic challenge. We report 2 patients with paraparesis caused by RDD of the thoracic spine and a PRISMA-style systematic review., Case Description: There were 2 patients with isolated extranodal thoracic spinal RDD without cervical lymphadenopathy. One patient presented with anterior thoracic RDD and a subtotal resection. The small residual disease completely responded to the postoperative course of steroids. The second patient had extradural thoracic spine RDD, which was resected completely. A 6-month postoperative follow-up magnetic resonance imaging (MRI) scan showed local recurrence, which responded to radiation therapy. Five years follow-up of both patients showed normal neurologic functions and no recurrence on MRI scan surveillance., Conclusions: RDD is a rare occurrence and should be considered in the differential diagnosis of extradural or intradural spinal lesions. Gross total resection is recommended, and long-term clinical follow-up with MRI is advised. Residual or recurrent RDD requires steroids or radiation therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

About half of acute stroke patients treated with mechanical thrombectomy (MT) do not show clinical improvement despite successful recanalization. Early arterial reocclusion (EAR) may be one of the causes that explain this phenomenon. We aimed to analyze the incidence and clinico-radiological correlations of EAR after successful MT. A consecutive series of patients treated with MT between 2010 and 2018 at a single-center included in a prospective registry was retrospectively reviewed. Specific inclusion criteria for the analysis were (1) successful recanalization after MT and (2) availability of pretreatment CT perfusion and follow-up MRI. EAR was evaluated in the follow-up MR angiography. Adjusted regression models were used to analyze the association of EAR with pretreatment variables, infarct growth, final infarct volume, and clinical outcome at 90 days (ordinal distribution of the modified Rankin Scale scores). Out of 831 MT performed, 218 (26%) patients fulfilled inclusion criteria, from whom 13 (6%) suffered EAR. In multivariate analysis controlled by confounders, EAR was independently associated with poor clinical outcome (aOR = 3.2, 95%CI = 1.16-9.72, p = 0.039), greater final infarct volume (aOR = 3.8, 95%CI = 1.93-7.49, p < 0.001), and increased infarct growth (aOR = 8.5, CI95% = 2.04-34.70, p = 0.003). According to mediation analyses, the association between EAR and poor clinical outcome was mainly explained through its effects on final infarct volume and infarct growth. Additionally, EAR was associated with non-cardioembolic etiology (adjusted Odds Ratio (aOR) = 10.1, 95%CI = 1.25-81.35, p = 0.030) and longer procedural time (aOR = 2.6, 95%CI = 1.31-5.40, p = 0.007). Although uncommon, EAR hampers the benefits of successful recanalization after MT resulting in increased infarct growth and larger final lesions.

Information on microstructural white matter integrity has been shown to explain post-stroke recovery beyond clinical measures and focal brain damage. Especially, knowledge about early white matter changes might improve prediction of outcome. We investigated 42 acute reperfused ischemic stroke patients (mean age 66.5 years, 40% female, median admission NIHSS 9.5) with a symptomatic MRI-confirmed unilateral middle cerebral artery territory infarction 24-72 h post-stroke and after 3 months. All patients underwent neurological examination and brain MRI. Fifteen older healthy controls (mean age 57.3 years) were also scanned twice. We assessed fractional anisotropy (FA), mean diffusivity (MD), axial (AD), and radial diffusivity (RD). Patients showed significantly decreased white matter integrity in the hemisphere affected by the acute infarction 24-72 h post-stroke, which further decreased over 3 months compared with controls. Less decrease in FA of remote white matter tracts was associated with better stroke recovery even after correcting for infarct location and extent. A regression model including baseline information showed that the modified Rankin Scale and mean FA of the genu of the corpus callosum explained 53.5% of the variance of stroke recovery, without contribution of infarct volume. Furthermore, early dynamic FA changes of the corpus callosum within the first 3 months post-stroke independently predicted stroke recovery. Information from advanced MRI measures on white matter integrity at the acute stage, as well as early dynamic white matter degeneration beyond infarct location and extent, improve our understanding of post-stroke reorganization in the affected hemisphere and contribute to an improved prediction of recovery.

Whole-body MRI (WB-MRI) has evolved since its first introduction in the 1970s as an imaging technique to detect and survey disease across multiple sites and organ systems in the body. The development of diffusion-weighted MRI (DWI) has added a new dimension to the implementation of WB-MRI on modern scanners, offering excellent lesion-to-background contrast, while achieving acceptable spatial resolution to detect focal lesions 5 to 10 mm in size. MRI hardware and software advances have reduced acquisition times, with studies taking 40-50 min to complete.The rising awareness of medical radiation exposure coupled with the advantages of MRI has resulted in increased utilization of WB-MRI in oncology, paediatrics, rheumatological and musculoskeletal conditions and more recently in population screening. There is recognition that WB-MRI can be used to track disease evolution and monitor response heterogeneity in patients with cancer. There are also opportunities to combine WB-MRI with molecular imaging on PET-MRI systems to harness the strengths of hybrid imaging. The advent of artificial intelligence and machine learning will shorten image acquisition times and image analyses, making the technique more competitive against other imaging technologies.

Takotsubo cardiomyopathy (TC) is a reversible condition in which there is transient left ventricular (LV) dysfunction characterised most commonly by basal hyperkinesis and mid-apical LV ballooning and hypokinesia. It is said to be triggered by stress and mimics, such as acute coronary syndrome (ACS) clinically. Diagnosis is usually suspected on echocardiography due to the characteristic contraction pattern in a patient with symptoms and signs of ACS but normal coronary arteries on catheter angiography. Cardiac magnetic resonance (CMR), with its latest advancements, is the diagnostic modality of choice for diagnosis, prognosis and follow-up of patients. The advances in CMR (including T1, T2, ECV mapping and threshold-based late gadolinium enhancement (LGE) measurements have revolutionised the role of CMR in tissue characterisation and prognostication in patients with TC. In this review, we highlight the current role of CMR in management of TC and enumerate the CMR findings in TC as well the current advances in the field of CMR, which could help in prognosticating these patients.

Aortic valve stenosis (AS) is a common valvular heart disease. Recently, transcatheter aortic valve implantation (TAVI) has changed the treatment of severe AS in elderly patients with contraindications to traditional surgical replacement. Echocardiography is conventionally used as the first imaging modality to assess the presence and severity of AS and to provide anatomical and functional information. Nowadays, imaging techniques play a crucial role in the planning of TAVI to define suitable candidates. Computed tomography (CT) is essential to display the anatomy of the aortic valve complex (including aortic annulus, Valsalva sinuses, coronary arteries ostia, sinotubular junction), thoracoabdominal aorta, and vascular access. Cardiac CT may also provide the evaluation of coronary arteries in alternative to conventional coronary angiography. Magnetic resonance imaging may be alternative or supplementary in selected cases, providing detailed information of cardiac function and myocardial wall characteristics. More recently, advanced computer modeling image-based techniques can be used to support the evaluation of the feasibility and safety of TAVI procedures.

Rationale: Previous studies have suggested that chronic cannabis use has been associated with increased blood oxygen level-dependent (BOLD) response during a response inhibition task; however, these studies primarily included males., Objectives: We investigated whether gender moderated the effects of cannabis use on BOLD response and behavioral performance during a Go-NoGo task in adolescents and young adults following 2 weeks of monitored abstinence., Methods: Participants included 77 16-26-year olds (MJ = 36, controls = 41). An emotion-based Go-NoGo task required participants to inhibit their response during a calm face. A whole-brain analysis looked at differences between cannabis group, gender, and their interaction., Results: Significant greater BOLD responses were observed in cannabis users compared with that in controls in the left frontal cortex, left cingulate cortex, and the left thalamus during correct response inhibitions; gender did not moderate these effects., Conclusion: Supporting previous research, cannabis users showed greater BOLD responses in core areas associated with response inhibition during a Go-NoGo task, even after a minimum of 2 weeks of abstinence.

Using the Medicare Physician-Supplier Procedure Summary Master File, we evaluated the evolving use of fMRI in Medicare fee-for-service beneficiaries from 2007 through 2017. Annual use rates (per 1,000,000 enrollees) increased from 17.7 to 32.8 through 2014 and have remained static since. Radiologists have remained the dominant specialty group from 2007 to 2017 (86.4% and 88.6% of all services, respectively), and the outpatient setting has remained the dominant place of service (65.4% and 65.4%, respectively)., (© 2020 by American Journal of Neuroradiology.)

Purpose: The purported underutilization of magnetoencephalography (MEG) among the USA epilepsy centers has never been studied, and any evidence-based understanding of its magnitude is lacking., Methods: Two hundred twenty-five National Association of Epilepsy Centers centers (2016) were invited to participate anonymously in a 13-question web-based survey of clinical practice focused on MEG use., Results: On average, centers (N = 70; 61 of which were level 4) reported <6 epileptologists, >7 dedicated epilepsy monitoring unit beds, 206 phase 1 studies, 15 phase 2 studies, 10 direct resections, and 9 indirect resections; 27% owned MEG. On average, 11.2 MEGs per year were ordered for epilepsy localization and 7.6 for any presurgical mapping modalities. Wada test aka the intracarotid sodium amobarbital procedure (ISAP) (43%) and functional MRI (29%) were preferred over MEG (4%) for language mapping. The number of epileptologists and the number of epilepsy monitoring unit beds correlated positively with the most clinical volumes. The centers who own a MEG had surgical volumes significantly higher than those without. The number and complexity of patients as well as the proximity of a MEG were perceived as significant contributors/obstacles to increased MEG use., Conclusions: Only the centers with larger surgical volumes incorporate MEG regularly in presurgical evaluation of patients with drug-resistant epilepsy. A reversal of the pervasive underutilization of epilepsy surgery can benefit from MEG, but this requires a sustained concerted promotion by the epilepsy and MEG communities.

Objective: To characterize seizure and cognitive outcomes of sparing vs removing an magnetic resonance imaging (MRI)-normal hippocampus in patients with temporal lobe epilepsy., Methods: In this retrospective cohort study, we reviewed clinical, imaging, surgical, and histopathological data on 152 individuals with temporal lobe epilepsy and nonlesional hippocampi categorized into hippocampus-spared (n = 74) or hippocampus-resected (n = 78). Extra-hippocampal lesions were allowed. Pre- and postoperative cognitive data were available on 86 patients. Predictors of seizure and cognitive outcomes were identified using Cox-proportional hazard modeling followed by treatment-specific model reduction according to Akaike information criterion, and built into an online risk calculator., Results: Seizures recurred in 40% within one postoperative year, and in 63% within six postoperative years. Male gender (P = .03), longer epilepsy duration (P < .01), normal MRI (P = .04), invasive evaluation (P = .02), and acute postoperative seizures (P < .01) were associated with a higher risk of recurrence. We found no significant difference in postoperative seizure freedom rates at 5 years between those whose hippocampus was spared and those whose hippocampus was resected (P = .17). Seizure outcome models built with pre- and postoperative data had bootstrap validated concordance indices of 0.65 and 0.72. The dominant hippocampus-spared group had lower rates of decline in verbal memory (39% vs 70%; P = .03) and naming (41% vs 79%; P = .01) compared to the hippocampus-resected group. Partial hippocampus sparing had the same risk of verbal memory decline as for complete removal., Significance: Sparing or removing an MRI-normal hippocampus yielded similar long-term seizure outcome. A more conservative approach, sparing the hippocampus, only partially shields patients from postoperative cognitive deficits. Risk calculators are provided to facilitate clinical counseling., (© 2020 International League Against Epilepsy.)

We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein. Brain imaging at 7 T was used to segment cortical and white matter lesions and 3 T imaging for cortical thickness estimation. Cervical spinal cord lesions were mapped voxel-wise as a function of distance from the inner central canal CSF pool to the outer subpial surface. Similarly, brain white matter lesions were mapped voxel-wise as a function of distance from the ventricular system. Subjects with relapsing-remitting multiple sclerosis showed a greater predominance of spinal cord lesions nearer the outer subpial surface compared to secondary progressive cases. Inversely, secondary progressive participants presented with more centrally located lesions. Within the brain, there was a strong gradient of lesion formation nearest the ventricular system that was most evident in participants with secondary progressive multiple sclerosis. Lesion fractions within the spinal cord grey and white matter were related to the lesion fraction in cerebral white matter. Cortical thinning was the primary determinant of the Expanded Disability Status Scale, white matter lesion fractions in the spinal cord and brain of the 9-Hole Peg Test and cortical thickness and spinal cord grey matter cross-sectional area of the Timed 25-Foot Walk. Spinal cord lesions were localized nearest the subpial surfaces for those with relapsing-remitting and the central canal CSF surface in progressive disease, possibly implying CSF-mediated pathogenic mechanisms in lesion development that may differ between multiple sclerosis subtypes. These findings show that spinal cord lesions involve both grey and white matter from the early multiple sclerosis stages and occur mostly independent from brain pathology. Despite the prevalence of cervical spinal cord lesions and atrophy, brain pathology seems more strongly related to physical disability as measured by the Expanded Disability Status Scale., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)