MRI quantitative muscle characterization in children with X-linked hypophosphatemia.

INTRODUCTION: Children with X Linked Hypophosphatemia (XLH) suffer from carential ricket, bone deformities and lameness. No previous study demonstrated a morphological distinction in muscles in these patients. The aim of this prospective study was to characterize, using Magnetic Resonance Imaging (MRI), the muscle morphology of pelvis, thigh and leg in children with XLH and to compare it with typically developed (TD) children. HYPOTHESIS: We hypothesized that lower limbs muscles in children with XLH are different from TD children and could explain limp walking. MATERIAL AND METHODS: Three-dimensional reconstructions of the muscles were performed in 11 patients with XLH and 15 TD children. Muscle lengths, sections and volumes were calculated and normalized with height and weight. Mean age was 10. RESULTS: Lengths were all smaller in children with XLH except for the Medius/minimus gluteus muscles (p=0.64). The difference seemed higher in muscles with a long tendinous part as semitendinosus (0.139 vs 0,164; p<0.01). All volumes were significantly inferior in children with XLH. This preliminary study showed significant differences in muscle structures between patients with XLH and TD children. DISCUSSION: Medius/minimus gluteus seemed to be particularly developed in children with XLH. Nevertheless it is not possible to conclude if it is related to XLH or a consequence of bone deformities. LEVEL OF PROOF: IV.

Combined gait analysis and radiologic examination in children with X-linked hypophosphatemia.

BACKGROUND: X-linked hypophosphataemia causes bone deformities and gait abnormalities that tend to worsen with age in the absence of appropriate treatment. However, doctors do not currently use quantitative tools to characterize these symptoms and their possible interactions. METHODS: Radiographs and 3D gait data from 43 non-surgical growing children with X-linked hypophosphataemia were acquired prospectively. Data from age-matched typically developing children were used to form the reference group. Subgroups based on radiological parameters were compared with each other and with the reference population. Linear correlations between radiographic parameters and gait variables were examined. FINDING: X-linked hypophosphatemic patients differed from the control group in pelvic tilt, ankle plantarflexion, knee flexion moment and power. High correlations with tibiofemoral angle were found for trunk lean, knee and hip adduction, and knee abduction moment. The Gait Deviation Index was below 80 for 88% of the patients with a high tibiofemoral angle (varus). Compared to other subgroups, varus patients had augmented trunk lean (+3°) and knee adduction (+10°) and decreased hip adduction (-5°) and ankle plantarflexion (-6°). Femoral torsion was associated with alterations in rotation at the knee, and hip. INTERPRETATION: Gait abnormalities induced in X-linked hypophosphataemia have been described in a large cohort of children. Links between gait alterations and lower limb deformities were found, with varus deformities standing out. Since bony deformities appear when X-linked hypophosphatemic children start walking and have been found to alter gait patterns, we suggest that combining radiology with gait analysis may improve the clinical management of X-linked hypophosphataemia.

Changes in adipose bone marrow and bone morphology in X-linked hypophosphatemic rickets.

INTRODUCTION: X-linked hypophosphatemic (XLH) rickets causes significant bone deformities in the lower limbs resulting from a bone mineralization defect. According to Frost's Mechanostat theory, compensatory modeling of the bones takes place during increased mechanical loads. In addition, mechanical stimuli modulate the differentiation of mesenchymal stem cells; common precursors to bone marrow adipocytes and osteoblasts. HYPOTHESIS: Bone deformities of the lower limbs lead to increased femoral bone mass and decreased fatty infiltration of the bone marrow (FIBM) in children with XLH rickets compared to a control group. PATIENTS AND METHODS: Eleven children (10.3years [6-17]) with XLH rickets and 22 healthy children (10.2years [5-15.5]) underwent lower limb Magnetic Resonance Imaging. A calculation of FIBM was performed at the mid-femur, as well as a calculation of the total bone cross-sectional area (CSA), the cortical CSA, the anteroposterior and mediolateral axes of the femur, bone marrow and the thickness of the femoral cortices. RESULTS: Total bone CSA, total cortical CSA and bone marrow CSA were higher in the XLH group than in the control group (p<0.05). The mid-lateral diameters of the femur and bone marrow were more elongated than those of the control group (p<0.001). Only the anterior cortex was thinned in the XLH group (p=0.001), while there was no difference with the control group for the posterior, medial and lateral cortices. The total percentage of FIBM was 72.81% [±3.95] and 77.4% [±5.52] for the XLH and control groups respectively (p<0.001). DISCUSSION: The increase in bone mass in the XLH population reflects an adaptation of bone tissue to the bone deformities present in this pathology. The decrease in FIBM indicates a lower risk of osteoporosis in the XLH population and may constitute a new monitoring parameter in this pathology. LEVEL OF STUDY: III; Case-control study.

Quantitative analysis of lower limb and pelvic deformities in children with X-linked hypophosphatemic rickets.

INTRODUCTION: X-linked hypophosphatemia (XLH) rickets mainly causes leg deformities in children that can worsen as they grow. We hypothesized that quantifying the bone parameters will help to document and monitor these deformities in children with XLH. METHODS: Thirty-five growing children affected by XLH were included in this cross-sectional study. Biplanar radiographs were taken with an EOS system allowing three-dimensional (3D) reconstructions of the pelvis and legs. Sixteen geometric parameters were calculated for the legs and pelvis. A control group of 40 age-matched patients was used to define the reference values for these geometric parameters. RESULTS: For the legs, significant differences (p<0.05) appeared between the XLH patients and the control group in the neck-shaft angle, femur/tibia length ratio and HKS. Among the 70 legs in the XLH group, 23 were in genu varum, 25 were in genu valgum and 22 were straight. There were significant differences between the genu varum and genu valgum subgroups in the femoral mechanical angle and the HKS. A strong correlation was found between the femoral mechanical angle and femorotibial angle (r2=0.73) and between the femoral mechanical angle and HKS (r2=0.69) The sacral slope and acetabular anteversion were significant different from the reference values. DISCUSSION: Quantitative radiological parameters derived from 3D reconstructions show that the deformities in XLH patients are (1) mainly in - but not limited to - the femoral shaft; (2) highly variable from one person to another. Some of these radiological parameters may be useful for the diagnosis and monitoring of XLH patients. LEVEL OF EVIDENCE: III; case control study.

Prospective Analysis of Muscle Adiposity in Children With X-linked Hypophosphatemic Rickets vs Control Children.

Context: Children with X-linked hypophosphatemic (XLH) rickets have muscle weakness that severely impairs their function. Intermuscular and intramuscular adipose tissue (IMAT and intraMAT, respectively) may contribute to this muscle weakness. Objective: This work aimed to compare IMAT and intraMAT in XLH children vs typically developing (TD) children. Methods: A prospective, monocentric cohort study was conducted of XLH (n = 11; aged 10.3 years [6-17]) and TD children (n = 22; aged 10.2 years [5-15.5]). All children underwent magnetic resonance imaging of the lower limbs; IMAT and intraMAT percentages were calculated after manual contouring of each muscle of the thigh and the deep fascia at mid-thigh level. Results: XLH children were comparable in age but shorter and heavier than TD children (P = .001 and P = .03, respectively). They had smaller muscle length and volume than TD children (P < .001) but there was no statistically significant difference in muscle cross-sectional area between the groups (P = .833). The total percentage of IMAT was higher in XLH children (8.66% vs 3.60% in TD children; P < .0001). In addition, though the total percentage of intraMAT did not differ significantly (12.58% and 10.85% in XLH and TD children, respectively; P = .143) intraMAT was statistically significantly higher in XLH children than TD children in 4 of the 13 muscles studied. Conclusion: Our results show that IMAT is higher in young children with XLH, independently of obesity and overweight. Further, these results will facilitate both the early prevention of functional and metabolic consequences of the increase in adipose tissue in XLH children.

Assessment of a novel deep learning-based marker-less motion capture system for gait study.

BACKGROUND: Marker-less systems based on digital video cameras and deep learning for gait analysis could have a deep impact in clinical routine. A recently developed system has shown promising results in terms of joint center position but has not been yet evaluated in terms of gait outcomes. RESEARCH QUESTION: How does this novel marker-less system compare to a marker-based reference system in terms of clinically relevant gait parameters? METHODS: The deep learning method behind the developed marker-less system was trained on a dedicated dataset consisting of forty-one asymptomatic and pathological subjects each performing ten walking trials. The system could estimate the three-dimensional position of seventeen joint centers or keypoints (e.g., neck, shoulders, hip, knee, and ankles). We evaluated the marker-less system against a marker-based system in terms of differences in joint position (Euclidean distance), detection of gait events (e.g., heel strike and toe-off), spatiotemporal parameters (e.g., step length, time), kinematic parameters (e.g., hip and knee extension-flexion), and inter-trial reliability for kinematic parameters. RESULTS: The marker-less system was able to estimate the three-dimensional position of joint centers with a mean difference of 13.1 mm (SD = 10.2 mm). 99% of the estimated gait events were estimated within 10 ms of the corresponding reference values. Estimated spatiotemporal parameters showed zero bias. The mean and standard deviation of the differences of the estimated kinematic parameters varied by parameter (for example, the mean and standard deviation for knee extension flexion angle were -3.0° and 2.7°). Inter-trial reliability of the measured parameters was similar to that of the marker-based references. SIGNIFICANCE: The developed marker-less system can measure the spatiotemporal parameters within the range of the minimum detectable changes obtained using the marker-based reference system. Moreover, except for hip extension flexion, the system showed promising results in terms of several kinematic parameters.

Fast quasi-automated 3D reconstruction of lower limbs from low dose biplanar radiographs using statistical shape models and contour matching.

Three-dimensional bone reconstructions from medical imaging are essential for biomechanical modelling and are growing tools in clinics. Several methods of lower limbs reconstruction from biplanar radiographs have been proposed in the literature but with significant operator dependence. A novel reconstruction method based on reduced manual annotation, statistical shape models and fully automatic adjustments was proposed in this study. While significantly reducing operator intervention, the proposed method demonstrated similar or better precision than previous approaches on clinical parameters. Meanwhile, shape accuracy was improved to around 1mm. By quasi-automating the 3D reconstruction without loss of accuracy and precision, the proposed approach is a considerable step towards extensive use of 3D personalized models in clinical routine and large cohort biomechanical studies.

A novel dataset and deep learning-based approach for marker-less motion capture during gait.

BACKGROUND: The deep learning-based human pose estimation methods, which can estimate joint centers position, have achieved promising results on the publicly available human pose datasets (e.g., Human3.6 M). However, these datasets may be less efficient for gait study, particularly for clinical applications, because of the limited number of subjects, their homogeneity (all asymptomatic adults), and the errors introduced by marker placement on subjects' regular clothing. RESEARCH QUESTION: How a new human pose dataset, adapted for gait study, could contribute to the advancement and evaluation of marker-less motion capture systems? METHODS: A marker-less system, based on deep learning-based pose estimation methods, was proposed. A new dataset (ENSAM dataset) was collected. Twenty-two asymptomatic adults, one adult with scoliosis, one adult with spondylolisthesis, and seven children with bone disease performed ten walking trials, while being recorded both by the proposed marker-less system and a reference system - combining a marker-based motion capture system and a medical imaging system (EOS). The dataset was split into training and test sets. The pose estimation method, already trained on the Human3.6 M dataset, was evaluated on the ENSAM test set, then reevaluated after further training on the ENSAM training set. The joints coordinates were evaluated, using Bland-Altman bias and 95 % confidence interval, and joint position error (the Euclidean distance between the estimated joint centers and the corresponding reference values). RESULTS: The Bland-Altman 95 % confidence intervals were substantially improved after finetuning the pose estimation method on the ENSAM training set (e.g., from 106.9 mm to 17.4 mm for the hip joint). With the new dataset and approach, the mean joint position error varied from 6.2 mm for ankles to 21.1 mm for shoulders. SIGNIFICANCE: The proposed marker-less system achieved promising results in terms of joint position errors. Future studies are necessary to assess the system in terms of gait parameters.

Combined 3D analysis of lower-limb morphology and function in children with idiopathic equinovarus clubfoot: A preliminary study.

INTRODUCTION: In children treated for idiopathic equinovarus clubfoot (EVCF), the relation between morphologic defects on clinical examination and standard X-ray on the one hand and functional abnormalities on the other is difficult to objectify. The aim of the present study was to demonstrate the feasibility of combined 3D analysis of the foot and lower limb based on biplanar EOS radiographs and gait analysis. The study hypothesis was that this provides better understanding of abnormalities in form and function. METHODS: Ten children with unilateral EVCF and "very good" clinical results were included. They underwent gait analysis on the Rizzoli Institute multisegment foot model. Kinematic data were collected for the hip, knee, ankle and foot (hindfoot/midfoot, midfoot/forefoot and hindfoot/forefoot). Biplanar EOS radiographs were taken to determine anatomic landmarks and radiological parameters. RESULTS: Complete acquisition time was around 2hours per patient. No significant differences were found between EVCF and healthy feet except for calcaneal incidence, tibiocalcaneal angle and hindfoot/midfoot and hindfoot/forefoot inversion. DISCUSSION: The feasibility of the combined analysis was confirmed. There were no differences in range of motion, moment or power between EVCF and healthy feet in this series of patients with very good results. The functional results are related to radiological results within the normal range. The protocol provided anatomic and kinematic reference data. A larger-scale study could more objectively assess the contribution of EOS radiography using optoelectronic markers. LEVEL OF EVIDENCE: II, low-power prospective study.