Publications

Regular exercise using assistive movement devices, such as running frames, has emerged as a promising strategy to improve cardiorespiratory fitness in individuals with cerebral palsy (CP). However, the molecular pathways underlying these adaptations remain poorly understood. Here, we examined a novel class of signalling molecules, mitochondrial-derived microproteins (MDPs), and assessed whether individuals with CP exhibit altered circulating levels compared with typically developing (TD) individuals at rest and following an acute bout of endurance exercise. Three groups were included: TD adults (31 ± 6 years), TD adolescents (16 ± 1 years) and adults with CP (25 ± 6 years). Individuals with CP were classified as Gross Motor Function Classification System (GMFCS) levels II−IV and had at least 3 months of frame running experience. Habitual physical activity, ultrasound-derived muscle thickness, and peak oxygen uptake were assessed. The exercise session consisted of 45 min of frame running for individuals with CP and conventional running for TD participants. Blood samples were obtained before and 1 h after exercise, and plasma MDP concentrations were measured using in-house enzyme-linked immunosorbent assay. Adults with CP had reduced muscle mass and maximal oxygen uptake compared to TD individuals. Despite this, they exhibited basal circulating levels of MDPs, including humanin, MOTS-c and SHMOOSE, comparable to TD adults and adolescents, with no associations with CP subtype or motor impairment severity. Following exercise, circulating MDPs showed no or only modest changes across groups, with no differences between CP and TD individuals. Overall, these findings suggest preserved mitochondrial-derived signalling via MDPs in individuals with CP. View Publication

Background: Conventional advanced imaging for post-traumatic physeal bars of the distal tibia identifies abnormal ossification but provides limited information about the integrity of the remaining physis. This study sought to determine if diffusion tensor imaging (DTI) can noninvasively detect and quantify changes associated with the size of a post-traumatic physeal bar.

Methods: We conducted a single-center, retrospective, cross-sectional study of 16 pediatric patients (mean age: 11.8±1.5 y) with a radiographically confirmed unilateral post-traumatic physeal bar of the distal tibia. All patients underwent bilateral ankle MRI at 3.0 Tesla (T) with a DTI sequence. The contralateral healthy physis served as an internal control. Physeal bar size was quantified as a percentage of the total physeal cross-sectional area. Spearman correlation was used to assess the relationship between physeal bar size and DTI metrics, including fractional anisotropy (FA), apparent diffusion coefficient (ADC), and tractography-derived parameters.

Results: Physeal bar size demonstrated a strong positive correlation with FA within the region of interest (ρ=+0.71) and a strong negative correlation with ADC (ρ=-0.77) and radial diffusivity (ρ=-0.80). As bar size increased, tract count (ρ=-0.60) and tract volume (ρ=-0.65) on the affected side decreased significantly. Furthermore, physeal bar size strongly correlated with the magnitude of side-to-side asymmetry, particularly for the relative difference in tract volume (ρ=+0.76) and tract count (ρ=+0.74) between the injured and healthy ankles.

Conclusions: This preliminary study demonstrates that DTI can detect and quantify significant alterations in the distal tibial physis that correlate with the size of the physeal bar noted on conventional imaging. The observed changes in tissue anisotropy and diffusion tract metrics suggest that DTI may serve as a sensitive imaging biomarker for assessing the true extent of the physeal injury. This technique holds promise for enhancing the early diagnosis and monitoring of pediatric growth disturbances. View Publication

Objectives: To assess the diagnostic accuracy of chest CT for rib fractures in live children investigated for suspected physical abuse (SPA), using initial and follow-up chest radiographs (CXRs) as the reference standard.

Materials and methods: A retrospective 10-year (September 2011–2021) multicentre search was performed for children less than two years of age who received CXRs and chest CT for SPA. Nineteen consultant radiologists independently read the images: Round 1 (initial CXRs only), Round 2 (CTs only) and Round 3 (initial and follow-up CXRs). No reporter performed Round 3 before Round 1 or 2. Radiologists reported the presence of rib fractures, fracture age, fracture location and confidence level. CT diagnostic accuracy (sensitivity, specificity, and accuracy) was calculated per patient, per rib and per specific location along the rib arc.

Results: A total of 64 patients (36 boys) with a median age of 2 months were included and assessed by 19 independent consultant radiologists. Patient level analysis: CT sensitivity = 90.6% (95% confidence interval [CI]: 88.2–92.6), specificity = 74.2% (95% CI: 70.2–78.0). Rib level analysis: CT sensitivity = 85.6% (95% CI: 84.1–87.0), specificity = 94.16% (95% CI: 93.8–94.4). Location level analysis: CT sensitivity = 75.7% (95% CI: 74.0–77.4), specificity = 97.09% (95% CI: 96.9–97.2).

Conclusion: Chest CT confers accurate rib fracture detection in live children with SPA, with the potential to replace the current standard of performing six CXRs as part of initial and follow-up imaging for SPA. View publication

Age estimations are relevant for pre-trial detention, sentencing in criminal cases and as part of the evaluation in asylum processes to protect the rights and privileges of minors. No current method can determine an exact chronological age due to individual variations in biological development. This study seeks to develop a validated statistical model for estimating an age relative to key legal thresholds (15, 18, and 21 years) based on a skeletal (CT-clavicle, radiography-hand/wrist or MR-knee) and tooth (radiography-third molar) developmental stages. The whole model is based on 34 scientific studies, divided into examinations of the hand/wrist (15 studies), clavicle (5 studies), distal femur (4 studies), and third molars (10 studies). In total, data from approximately 27,000 individuals have been incorporated and the model has subsequently been validated with data from 5,000 individuals. The core framework of the model is built upon transition analysis and is further developed by a combination of a type of parametric bootstrapping and Bayesian theory. Validation of the model includes testing the models on independent datasets of individuals with known ages and shows a high precision with separate populations aligning closely with the model’s predictions. The practical use of the complex statistical model requires a user-friendly tool to provide probabilities together with the margin of error. The assessment based on the model forms the medical component for the overall evaluation of an individual’s age. View publication

Purpose: To assess the growth plates of the knee in a healthy population of young adults and adolescents using DTI, and to correlate the findings with chronological age and skeletal maturation.

Methods: A prospective, cross-sectional study to assess the tibial and femoral growth plates with DTI in 155 healthy volunteers aged between 14.0 and 21 years old. Echo-planar DTI with 15 directions and b value of 0 and 600 s/mm² was performed on a 3 T whole-body scanner.

Results: A relationship was observed between chronological age and most DTI metrics (fractional anisotropy, mean diffusivity, and radial diffusivity), tract length and volume. (No significant relationship could be seen for axonal diffusivity and tract length.) Subdivision according to skeletal maturation showed the greatest tract lengths and volumes seen in stage 4b and not 4a. The intra-observer agreement was significant (P = 0.01) for all the measured variables, but agreement varied (femur 0.53 – 0.98; tibia 0.58 – 0.98). Spearman’s correlation showed a significant correlation for age (P = 0.05; P = 0.01) as well as for the fractional anisotropy value within all variables in both femur and tibia. Tract number and volume had a similar correlation with most variables, especially the DTI metrics, and would seem to be interchangeable.

Conclusion: The current study indicates that DTI metrics could be a tool to assess the skeletal maturation process of the growth plate and its activity. Tractography seems promising to assess the activity of the growth plate in a younger population but must be used with caution in the more mature growth plate. View publication

Purpose: To assess the ability of MRI‐DTI to evaluate growth plate morphology and activity compared with that of histomorphometry and micro‐CT in rabbits.

Methods: The hind limbs of female rabbits aged 16, 20, and 24 wk (n = 4 per age group) were studied using a 9.4T MRI scanner with a multi‐gradient echo 3D sequence and DTI in 14 directions (b‐value = 984 s/mm²). After MRI, the right and left hind limb were processed for histological analysis and micro‐CT, respectively. The Wilcoxon signed‐rank test was used to evaluate the height and volume of the growth plate. Intraclass correlation and Pearson correlation coefficient were used to evaluate the association between DTI metrics and age.

Results: The growth plate height and volume were similar for all modalities at each time point and age. Age was correlated with all tractography and DTI metrics in both the femur and tibia. A correlation was also observed between all the metrics at both sites. Tract number and volume declined with age; however, tract length did not show any changes. The fractional anisotropy color map showed lateral diffusion centrally in the growth plate and perpendicular diffusion in the hypertrophic zone, as verified by histology and micro‐CT.

Conclusion: MRI‐DTI may be useful for evaluating the growth plates. View publication

Background: Bone age assessment (BAA) is used in numerous pediatric clinical settings as well as in legal settings when entities need an estimate of chronological age (CA) when valid documents are lacking. The latter case presents itself as critical as the law is harsher for adults and granted rights along with imputability changes drastically if the individual is a minor. Traditional BAA methods have drawbacks such as exposure of minors to radiation, they do not consider factors that might affect the bone age, and they mostly focus on a single region. Given the critical scenarios in which BAA can affect the lives of young individuals, it is important to focus on the drawbacks of the traditional methods and investigate the potential of estimating CA through BAA.

Objective: This study aims to investigate CA estimation through BAA in young individuals aged 14-21 years with machine learning methods, addressing the drawbacks of research using magnetic resonance imaging (MRI), assessment of multiple regions of interest, and other factors that may affect the bone age.

Methods: MRI examinations of the radius, distal tibia, proximal tibia, distal femur, and calcaneus were performed on 465 men and 473 women (aged 14-21 years). Measures of weight and height were taken from the subjects, and a questionnaire was given for additional information (self-assessed Tanner Scale, physical activity level, parents' origin, and type of residence during upbringing). Two pediatric radiologists independently assessed the MRI images to evaluate their stage of bone development (blinded to age, gender, and each other). All the gathered information was used in training machine learning models for CA estimation and minor versus adult classification (threshold of 18 years). Different machine learning methods were investigated.

Results: The minor versus adult classification produced accuracies of 0.90 and 0.84 for male and female subjects, respectively, with high recalls for the classification of minors. The CA estimation for the 8 age groups (aged 14-21 years) achieved mean absolute errors of 0.95 years and 1.24 years for male and female subjects, respectively. However, for the latter, a lower error occurred only for the ages of 14 and 15 years.

Conclusions: This study investigates CA estimation through BAA using machine learning methods in 2 ways: minor versus adult classification and CA estimation in 8 age groups (aged 14-21 years), while addressing the drawbacks in the research on BAA. The first achieved good results; however, for the second case, the BAA was not precise enough for the classification. View publication

Introduction: The development of efficient resistance exercise protocols to counteract muscle dysfunction in cerebral palsy is warranted. Whether individuals with cerebral palsy are able to perform iso-inertial resistance (flywheel) exercise in a comparable manner to typically developed subjects has never been experimentally tested.

Design: A comparative, controlled study. Subjects: Eight young ambulatory adults with cerebral palsy (mean age 19 years; Gross Motor Function Classification System (GMFCS) I?III) and 8 typically developed control subjects (mean age 21 years).

Methods: Subjects performed acute bouts on the weight-stack and flywheel leg-press device, respectively. Range of motion, electromyography, power, work and muscle thickness (ultrasound) data were collected.

Results: Subjects with cerebral palsy were able to produce a greater eccentric/concentric peak power ratio on the flywheel (p?<?0.05 vs ratio in weight-stack), however absolute values were lower (p?<?0.05 vs weight-stack). Typically developed subjects produced more power per mm of thigh muscle than the cerebral palsy group, independent of leg, device and action.

Discussion: Subjects with cerebral palsy could not elicit the eccentric overload seen in typically developed subjects. Furthermore, peak power production per mm muscle was markedly reduced in both legs in subjects with cerebral palsy. In conclusion, this comparative study of weight-stack and flywheel exercise does not support the implementation of the current iso-inertial protocol for young adults with cerebral palsy. View publication

Background: Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown.

Methods: Fifteen adolescents/young adults (mean age 16, range 9–29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period.

Results: Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p < 0.001). Average and maximum heart rate and Borg-RPE during the 6-MRT did not differ pre vs. post training. Thickness of the medial gastrocnemius muscle increased 9% in response to training (p < 0.05) on the more-affected side. Passive hip flexion increased (p < 0.05) on the less-affected side and ankle dorsiflexion decreased (p < 0.05) on the more affected side after 12 weeks of RaceRunning training.

Conclusions: These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations. View publication