Repetitive head impact (RHI) exposure in collision sports may contribute to adverse neurological outcomes in former players. In contrast to a concussion, or mild traumatic brain injury, "subconcussive" RHIs represent a more frequent and asymptomatic form of exposure. The neural network-level signatures characterizing subconcussive RHIs in youth collision-sport cohorts such as American Football are not known. Here, we used resting-state functional MRI to examine default mode network (DMN) functional connectivity (FC) following a single football season in youth players (n = 50, ages 8-14) without concussion. Football players demonstrated reduced FC across widespread DMN regions compared with non-collision sport controls at postseason but not preseason. In a subsample from the original cohort (n = 17), players revealed a negative change in FC between preseason and postseason and a positive and compensatory change in FC during the offseason across the majority of DMN regions. Lastly, significant FC changes, including between preseason and postseason and between in-and off-season, were specific to players at the upper end of the head impact frequency distribution. These findings represent initial evidence of network-level FC abnormalities following repetitive, non-concussive RHIs in youth football. Furthermore, the number of subconcussive RHIs proved to be a key factor influencing DMN FC.
Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing.
OBJECTIVE Youth football athletes are exposed to repetitive subconcussive head impacts during normal participation in the sport, and there is increasing concern about the long-term effects of these impacts. The objective of the current study was to determine if strain-based cumulative exposure measures are superior to kinematic-based exposure measures for predicting imaging changes in the brain. METHODS This prospective, longitudinal cohort study was conducted from 2012 to 2017 and assessed youth, male football athletes. Kinematic data were collected at all practices and games from enrolled athletes participating in local youth football organizations in Winston-Salem, North Carolina, and were used to calculate multiple risk-weighted cumulative exposure (RWE) kinematic metrics and 36 strain-based exposure metrics. Pre- and postseason imaging was performed at Wake Forest School of Medicine, and diffusion tensor imaging (DTI) measures, including fractional anisotropy (FA), and its components (CL, CP, and CS), and mean diffusivity (MD), were investigated. Included participants were youth football players ranging in age from 9 to 13 years. Exclusion criteria included any history of previous neurological illness, psychiatric illness, brain tumor, concussion within the past 6 months, and/or contraindication to MRI. RESULTS A total of 95 male athletes (mean age 11.9 years [SD 1.0 years]) participated between 2012 and 2017, with some participating for multiple seasons, resulting in 116 unique athlete-seasons. Regression analysis revealed statistically significant linear relationships between the FA, linear coefficient (CL), and spherical coefficient (CS) and all strain exposure measures, and well as the planar coefficient (CP) and 8 strain measures. For the kinematic exposure measures, there were statistically significant relationships between FA and RWE linear (RWEL) and RWE combined probability (RWECP) as well as CS and RWEL. According to area under the receiver operating characteristic (ROC) curve (AUC) analysis, the best-performing metrics were all strain measures, and included metrics based on tensile, compressive, and shear strain. CONCLUSIONS Using ROC curves and AUC analysis, all exposure metrics were ranked in order of performance, and the results demonstrated that all the strain-based metrics performed better than any of the kinematic metrics, indicating that strain-based metrics are better discriminators of imaging changes than kinematic-based measures. Studies relating the biomechanics of head impacts with brain imaging and cognitive function may allow equipment designers, care providers, and organizations to prevent, identify, and treat injuries in order to make football a safer activity.
BACKGROUND AND PURPOSE: SWI is an advanced imaging modality that is especially useful in cerebral microhemorrhage detection. Such microhemorrhages have been identified in adult contact sport athletes, and the sequelae of these focal bleeds are thought to contribute to neurodegeneration. The purpose of this study was to utilize SWI to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are significantly greater than those of adolescent noncontact athletes.MATERIALS AND METHODS: Preseason and postseason SWI was performed and evaluated on 78 adolescent football players. SWI was also performed on 27 adolescent athletes who reported no contact sport history. Two separate one-tailed Fisher exact tests were performed to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are greater than those of noncontact athlete controls. RESULTS:Microhemorrhages were observed in 12 football players. No microhemorrhages were observed in any controls. Adolescent football players demonstrated a significantly greater prevalence of microhemorrhages than adolescent noncontact controls (P ¼ .02). Although 2 football players developed new microhemorrhages during the season, microhemorrhage incidence during 1 football season was not statistically greater in the football population than in noncontact control athletes (P ¼ .55). CONCLUSIONS:Adolescent football players have a greater prevalence of microhemorrhages compared with adolescent athletes who have never engaged in contact sports. While microhemorrhage incidence during 1 season is not significantly greater in adolescent football players compared to adolescent controls, there is a temporal association between playing football and the appearance of new microhemorrhages. ABBREVIATION: SWI ¼ susceptibility weighted imaging M icrohemorrhages result in abnormal blood product and iron accumulation in the brain after vascular injury. Although microhemorrhages are commonly associated with hypertension, apolipoprotein E « 4 carrier status, and cerebral
MRI-guided high-intensity focused ultrasound thalamotomy is an incisionless therapy for essential tremor. To reduce adverse effects, the field has migrated to treating at approximately 2 mm above the anterior commissure-posterior commissure plane. We perform MRI-guided high intensity focused ultrasound with an advanced imaging targeting technique, four tract tractography. Four tract tractography uses diffusion tensor imaging to identify the critical white matter targets for tremor control, the decussating and non-decussating dentatorubrothalamic tracts, while the corticospinal tract and medial lemniscus are identified to be avoided. In some patients, four tract tractography identified a risk of damaging the medial lemniscus or corticospinal tract if treating at 2 mm superior to the anterior commissure-posterior commissure plane. In these patients, we chose to target 1.2-1.5 mm superior to the anterior commissure-posterior commissure plane. In these patients, post-operative imaging revealed that the focused ultrasound lesion extended into the posterior subthalamic area. This study sought to determine if patients with focused ultrasound lesions that extend into the posterior subthalamic area have greater tremor improvement than those without. 20 essential tremor patients underwent MRI-guided high intensity focused ultrasound and were retrospectively classified into two groups. Group 1 included patients with extension of the thalamic focused ultrasound lesion into the posterior subthalamic area. Group 2 included patients without extension of the thalamic focused ultrasound lesion into the posterior subthalamic area. For each patient, the percent change in postural tremor, kinetic tremor, and Archimedes spiral scores were calculated between baseline and a three-month follow-up. Two-tailed Wilcoxon rank sum tests were used to compare improvement in tremor scores, total number of sonications, thermal dose to achieve initial tremor response, and skull density ratio between groups. Group 1 had significantly greater postural, kinetic, and Archimedes spiral score percent improvement than Group 2 (p-values: 5.41 × 10−5, 4.87 × 10−4, and 5.41 × 10−5, respectively). Group 1 also required significantly fewer total sonications to control the tremor and a significantly lower thermal dose to achieve tremor response (p-values: 6.60 × 10−4 and 1.08 × 10−5, respectively). No significant group differences in skull density ratio were observed (p-value = 1.0). We do not advocate directly targeting the posterior subthalamic area with MRI-guided high-intensity focused ultrasound because the shape of the focused ultrasound lesion can result in a high risk of adverse effects. However, when focused ultrasound lesions naturally extend from the thalamus into the posterior subthalamic area, they provide greater tremor control than those that only involve the thalamus.
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