Cross-site harmonization of multi-shell diffusion MRI measures based on rotational invariant spherical harmonics (RISH).

Quantification methods based on the acquisition of diffusion magnetic resonance imaging (dMRI) with multiple diffusion weightings (e.g., multi-shell) are becoming increasingly applied to study the in-vivo brain. Compared to single-shell data for diffusion tensor imaging (DTI), multi-shell data allows to apply more complex models such as diffusion kurtosis imaging (DKI), which attempts to capture both diffusion hindrance and restriction effects, or biophysical models such as NODDI, which attempt to increase specificity by separating biophysical components. Because of the strong dependence of the dMRI signal on the measurement hardware, DKI and NODDI metrics show scanner and site differences, much like other dMRI metrics. These effects limit the implementation of multi-shell approaches in multicenter studies, which are needed to collect large sample sizes for robust analyses. Recently, a post-processing technique based on rotation invariant spherical harmonics (RISH) features was introduced to mitigate cross-scanner differences in DTI metrics. Unlike statistical harmonization methods, which require repeated application to every dMRI metric of choice, RISH harmonization is applied once on the raw data, and can be followed by any analysis. RISH features harmonization has been tested on DTI features but not its generalizability to harmonize multi-shell dMRI. In this work, we investigated whether performing the RISH features harmonization of multi-shell dMRI data removes cross-site differences in DKI and NODDI metrics while retaining longitudinal effects. To this end, 46 subjects underwent a longitudinal (up to 3 time points) two-shell dMRI protocol at 3 imaging sites. DKI and NODDI metrics were derived before and after harmonization and compared both at the whole brain level and at the voxel level. Then, the harmonization effects on cross-sectional and on longitudinal group differences were evaluated. RISH features averaged for each of the 3 sites exhibited prominent between-site differences in the frontal and posterior part of the brain. Statistically significant differences in fractional anisotropy, mean diffusivity and mean kurtosis were observed both at the whole brain and voxel level between all the acquisition sites before harmonization, but not after. The RISH method also proved effective to harmonize NODDI metrics, particularly in white matter. The RISH based harmonization maintained the magnitude and variance of longitudinal changes as compared to the non-harmonized data of all considered metrics. In conclusion, the application of RISH feature based harmonization to multi-shell dMRI data can be used to remove cross-site differences in DKI metrics and NODDI analyses, while retaining inherent relations between longitudinal acquisitions.

Changes in circulating microRNAs following head impacts in soccer.

AIM: To explore the short-term effects of accidental head impacts and repetitive headers on circulating microRNAs, accounting for the effects of high-intensity exercise alone. METHODS: Blood samples were collected from professional soccer players at rest. Repeat samples were drawn 1 h and 12 h after three conditions: (1) accidental head impacts in a match, (2) repetitive headers during training, and (3) high-intensity exercise. 89 samples were screened to detect microRNAs expressed after each exposure. Identified microRNAs were then validated in 98 samples to determine consistently deregulated microRNAs. Deregulated microRNAs were further explored using bioinformatics to identify target genes and characterize their involvement in biological pathways. RESULTS: Accidental head impacts led to deregulation of eight microRNAs that were unaffected by high-intensity exercise; target genes were linked to 12 specific signaling pathways, primarily regulating chromatin organization, Hedgehog and Wnt signaling. Repetitive headers led to deregulation of six microRNAs that were unaffected by high-intensity exercise; target genes were linked to one specific signaling pathway (TGF-ß). High-intensity exercise led to deregulation of seven microRNAs; target genes were linked to 31 specific signaling pathways. CONCLUSION: We identified microRNAs specific to accidental head impacts and repetitive headers in soccer, potentially being useful as brain injury biomarkers.

Neurofilament light and tau in serum after head-impact exposure in soccer.

Introduction: Blood-based biomarkers can provide valuable information on the effects of repetitive head impacts in sports. This study investigated if repetitive headers or accidental head impacts in soccer could cause structural brain injury, detected as an increase in serum neurofilament light (NfL) or tau.Methods: NfL and tau were measured in professional soccer players in pre-season. Then, the effect of three short-term exposures on biomarker levels was assessed: (1) high-intensity exercise, (2) repetitive headers, and (3) head impacts in a match.Results: We analyzed 354 samples and observed no effects on NfL from any of the three short-term exposures. Tau levels rose significantly from baseline to 1 h after (1) high-intensity exercise (Δ0.50 pg/mL, 95% CI 0.19-0.81, p < .01); the same was observed after (2) repetitive headers (Δ0.29 pg/mL, 95% CI 0.10-0.48, p < .01), but not after (3) accidental head-impact incidents (Δ0.36 pg/mL, 95% CI -0.02-0.74, p = .06). The highest absolute values were seen 1 h after high-intensity exercise (mean±SD, 1.92 ± 0.83 pg/mL).Conclusion: NfL and tau in serum were unaffected by head impacts in soccer. Importantly, tau levels seem to rise in response to exercise, emphasizing the need for control groups. Our findings highlight important characteristics and limitations when using these biomarkers in sports.

Head impact exposure in youth football-Are current interventions hitting the target?

Restrictions on heading in youth football have been implemented in some countries to limit head impact exposure. However, current interventions remain poorly guided by evidence. Our objective was to quantify heading exposure in youth football, assessing the effects of sex and age. Football matches played during an international youth football tournament with no heading restrictions were directly observed, including players from both sexes (11-19 years). The elite senior level was included for comparison, using video analysis. All heading events were registered, classified, and assigned to individual players. Heading rates were calculated for each sex and age group. We observed a total of 267 matches, corresponding to 4011 player hours (1927 player hours for females, 2083 player hours for males). Males headed more frequently than females (2.7 vs 1.8 headers/player hour; P < .001). Heading rates increased with age (ANOVA, P < .001), approaching the elite senior level for players 16 years and older. There was substantial variation within teams for all age and sex groups, with the widest range (1-18 headers) observed for girls aged 19. Girls younger than 12 years had the lowest exposure, with an average of <2 players per team heading the ball, each with 1-2 headers. In conclusion, age and sex influence head impact exposure in youth football, and warrants careful consideration when introducing injury prevention measures. Males are more frequently exposed than females, heading rates increase with age, and there is substantial variation between players. Heading is a rare event in the youngest age groups, especially among females.

Evaluation of an In-Ear Sensor for Quantifying Head Impacts in Youth Soccer.

BACKGROUND: Wearable sensor systems have the potential to quantify head kinematic responses of head impacts in soccer. However, on-field use of sensors (eg, accelerometers) remains challenging, owing to poor coupling to the head and difficulties discriminating low-severity direct head impacts from inertial loading of the head from human movements, such as jumping and landing. PURPOSE: To test the validity of an in-ear sensor for quantifying head impacts in youth soccer. STUDY DESIGN: Descriptive laboratory study. METHODS: First, the sensor was mounted to a Hybrid III headform and impacted with a linear impactor or a soccer ball. Peak linear acceleration (PLA), peak rotational acceleration (PRA), and peak rotational velocity (PRV) were obtained from both systems; random and systematic errors were calculated with Hybrid III as reference. Then, 6 youth soccer players wore sensors and performed a structured training protocol, including heading and nonheading exercises; they also completed 2 regular soccer sessions. For each accelerative event recorded, PLA, PRA, and PRV outputs were compared with video recordings. Receiver operating characteristic curves were used to determine the sensor's discriminatory capacity in both on-field settings, establishing cutoff values for predicting outcomes. RESULTS: For the laboratory tests, the random error was 11% for PLA, 20% for PRA, and 5% for PRV; the systematic error was 11%, 19%, and 5%, respectively. For the structured training protocol, heading events resulted in higher absolute values (PLA = 15.6 g± 11.8 g) than nonheading events (PLA = 4.6 g± 1.2 g); the area under the curve was 0.98 for PLA. In regular training sessions, the area under the curve was >0.99 for PLA. A 9 g cutoff value yielded a positive predictive value of 100% in the structured training protocol versus 65% in the regular soccer sessions. CONCLUSION: The in-ear sensor displayed considerable random error and substantially overestimated head impact exposure. Despite the sensor's excellent on-field accuracy for discriminating headings from other accelerative events in youth soccer, absolute values must be interpreted with caution, and there is a need for secondary means of verification (eg, video analysis) in real-life settings. CLINICAL RELEVANCE: Wearable sensor systems can potentially provide valuable insights into head impact exposures in contact sports, but their limitations require careful consideration.