DTI assessment of the maturing growth plate of the knee in adolescents and young adults.

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.

Automated localization of the medial clavicular epiphyseal cartilages using an object detection network: a step towards deep learning-based forensic age assessment.

BACKGROUND: Deep learning is a promising technique to improve radiological age assessment. However, expensive manual annotation by experts poses a bottleneck for creating large datasets to appropriately train deep neural networks. We propose an object detection approach to automatically annotate the medial clavicular epiphyseal cartilages in computed tomography (CT) scans. METHODS: The sternoclavicular joints were selected as structure-of-interest (SOI) in chest CT scans and served as an easy-to-identify proxy for the actual medial clavicular epiphyseal cartilages. CT slices containing the SOI were manually annotated with bounding boxes around the SOI. All slices in the training set were used to train the object detection network RetinaNet. Afterwards, the network was applied individually to all slices of the test scans for SOI detection. Bounding box and slice position of the detection with the highest classification score were used as the location estimate for the medial clavicular epiphyseal cartilages inside the CT scan. RESULTS: From 100 CT scans of 82 patients, 29,656 slices were used for training and 30,846 slices from 110 CT scans of 110 different patients for testing the object detection network. The location estimate from the deep learning approach for the SOI was in a correct slice in 97/110 (88%), misplaced by one slice in 5/110 (5%), and missing in 8/110 (7%) test scans. No estimate was misplaced by more than one slice. CONCLUSIONS: We demonstrated a robust automated approach for annotating the medial clavicular epiphyseal cartilages. This enables training and testing of deep neural networks for age assessment.

Application of 3D MAPs pipeline identifies the morphological sequence chondrocytes undergo and the regulatory role of GDF5 in this process.

The activity of epiphyseal growth plates, which drives long bone elongation, depends on extensive changes in chondrocyte size and shape during differentiation. Here, we develop a pipeline called 3D Morphometric Analysis for Phenotypic significance (3D MAPs), which combines light-sheet microscopy, segmentation algorithms and 3D morphometric analysis to characterize morphogenetic cellular behaviors while maintaining the spatial context of the growth plate. Using 3D MAPs, we create a 3D image database of hundreds of thousands of chondrocytes. Analysis reveals broad repertoire of morphological changes, growth strategies and cell organizations during differentiation. Moreover, identifying a reduction in Smad 1/5/9 activity together with multiple abnormalities in cell growth, shape and organization provides an explanation for the shortening of Gdf5 KO tibias. Overall, our findings provide insight into the morphological sequence that chondrocytes undergo during differentiation and highlight the ability of 3D MAPs to uncover cellular mechanisms that may regulate this process.

MRI assessment of growth disturbances after ACL reconstruction in children with open growth plates-Prospective multicenter study of 100 patients.

INTRODUCTION: We were interested in the consequences of anterior cruciate ligament (ACL) reconstruction on the growth plates and the impact on growth in children with open growth plates. The primary objective was related to growth disturbances with the null hypothesis being that ACL reconstruction in open growth plates does not cause any. The secondary objective related to the presence of physis lesions on MRI, with the null hypothesis being that ACL reconstruction in open growth plates does not induce any. MATERIAL AND METHODS: In the context of a 2017 SFA symposium on ACL reconstruction with open growth plates, we conducted a prospective multicenter study with 2 years' follow-up. The study enrolled 100 patients; 71 were available for analysis. Four reconstruction techniques were used: semitendinosus-gracilis (STG), short graft (SG), quadriceps tendon (QT) and fascia lata (FL). MRI was used to look for growth disturbances as evidenced by deviation of the Harris lines or modification of the physis and diaphysis angles. Physis lesions were determined on MRI based on the presence of physeal bone bridges (PBB). RESULTS: No growth disturbances were found. However, PBBs were found in 14 patients (20%). At the femur, the relative risk (RR) was higher when a STG graft was used (RR=2.1) and the tunnel diameter was≥9mm (RR=1.7). Epiphyseal fixation had a higher risk than transphyseal fixation (RR=1.6 vs. 1.2). At the tibia, the RR was higher when a QT graft was used (RR=3.6), when screw fixation was performed (RR=3.7) or when the graft did not fill the tunnel sufficiently (RR=1.5). DISCUSSION: The absence of growth disturbances after 2 years' follow-up validates the possibility of ACL reconstruction with open growth plates, including with transphyseal techniques. The presence of small growth plate lesions such as bone bridges means that precautions should be taken with respect to tunnel trajectory, tunnel diameter, graft and tunnel diameter matching and graft fixation. LEVEL OF EVIDENCE: III, prospective cohort study.

Validation of the ultrasonographic assessment of the femoral trochlea epiphyseal cartilage in foals at osteochondrosis predilected sites with magnetic resonance imaging and histology.

BACKGROUND: Noninvasive imaging tools are needed to screen foal femoropatellar joints to detect subclinical osteochondrosis lesions due to focal failure of endochondral ossification to enhance early management to optimise intrinsic healing events. Recently investigations employing 3T susceptibility-weighted magnetic resonance imaging (3T SWI MRI) and CT have demonstrated their capacity for early osteochondrosis diagnosis, but these technologies are not practical for field screening. We postulate that ultrasonography is a valuable field tool for the detection of subclinical osteochondrosis lesions. OBJECTIVES: The goals were to 1) describe the ultrasonographic features of the femoral trochlea of healthy and osteochondrosis-predisposed neonatal foals, 2) validate the capacity of ultrasound to assess cartilage canal vascular archictecture and the ossification front and 3) evaluate field feasibility in a pilot study. STUDY DESIGN: Experimental study. METHODS: Ultrasonographic evaluation of osteochondrosis predisposed (n = 10) and control (n = 6) femoral trochleas was performed ex vivo and compared with site-matched histological sections and 3T SWI MRI. The articular and epiphyseal cartilage thickness, ossification front indentation and cartilage canal vascular archictecture were assessed at each ROI. Femoral trochleae of foals (n = 3) aged ≈ 1, 3 and 6 months were also evaluated with ultrasonography in field. RESULTS: Ultrasonographic measurements strongly correlated with the histological measurements. There was no difference in the cartilage thickness or ossification front indentation between control and osteochondrosis-predisposed specimens. The cartilage canal vascular archictecture on ultrasonograms corresponded with the vessel pattern observed on site matched histology and 3T SWI MRI. MAIN LIMITATIONS: The number of specimens for study was limited and no early osteochondrosis lesions were present within the predilected group, but a field study is now underway. CONCLUSION: Ultrasonographic examination of the femoral trochlea permitted accurate evaluation of cartilage thickness, cartilage canal vascular archictecture and ossification front indentation in young foals and is a promising, practical tool for screening subclinical osteochondrosis and monitoring and managing lesions at important clinical sites.

Assessment of pharmacokinetics for microvessel proliferation by DCE-MRI for early detection of physeal bone bridge formation in an animal model.

OBJECTIVES: Bone bridge formation occurs after physeal lesions and can lead to growth arrest if not reversed. Previous investigations on the underlying mechanisms of this formation used histological methods. Therefore, this study aimed to apply a minimally invasive method using dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS: Changes in functional parameters related to the microvessel system were assessed in a longitudinal study of a cohort of an animal model applying a reference region model. The development of morphology of the injured physis was investigated with 3D high-resolution MRI. To acquire complementary information for MRI-related findings qRT-PCR and immunohistochemical data were acquired for a second cohort of the animal model. RESULTS: The evaluation of the pharmacokinetic parameters showed a first rise of the transfer coefficient 7 days post-lesion and a maximum 42 days after operation. The analysis of the complementary data showed a connection of the first rise to microvessel proliferation while the maximum value was linked to bone remodeling. CONCLUSION: The pharmacokinetic analysis of DCE-MRI provides information on a proliferation of microvessels during the healing process as a sign for bone bridge formation. Thereby, DCE-MRI could identify details, which up to now required analyses of highly invasive methods.

Assessment of skeletal age on the basis of DXA-derived hand scans in elite youth soccer.

Physical performance is highly dependent on maturity. Therefore, consideration of maturity is recommended in the talent identification process. To date, skeletal age (SA) is assessed using X-ray scans. However, X-rays are associated with a 10-fold higher radiation compared to dual-energy X-ray absorptiometry (DXA). The aim of the study was to validate SA assessments in male soccer players with the DXA technique. Paired X-ray and DXA scans of the left hand of 63 Swiss U-15 national soccer players were performed. SA assessments were performed twice by two blinded raters using Tanner and Whitehouse' reference technique. Intrarater and interrater reliability as well as agreement between both techniques were tested. Intrarater and interrater reliabilities were excellent. Bland-Altman plots showed that SA assessments between X-ray and DXA differed by -0.2 years and 95% limits of agreement were ±0.6 years. Therefore, DXA offered a replicable method for assessing SA and maturity in youth soccer players.

Tooth mineralization stages as a diagnostic tool for assessment of skeletal maturity.

INTRODUCTION: The objective of this study was to determine whether dental calcification can be used as a first-level diagnostic tool for assessment of skeletal maturity. METHODS: A total of 150 healthy subjects (79 boys, 71 girls; mean age, 12.19 ± 2.03 years; range, 8-16 years) were enrolled in the study. Dental maturity was assessed through the calcification stages from panoramic radiographs of the mandibular canine, the first and second premolars, and the second molar. Determination of skeletal maturity was according to the modified middle phalanx of third finger (MP3) stages method on digital radiographs. RESULTS: Diagnostic ability was evaluated according to the dental maturation stages for each tooth for identification of the MP3 stages and the growth phases (prepubertal, pubertal, postpubertal) using positive likelihood ratios. Dental maturation stage E of the first premolars and the combination of canine stage F, first premolar stage E, second premolar stage E, and second molar stage D (FEED) gave the highest values for identification of the prepubertal growth phase, and stage H of the second molar had the highest value for identification of the postpubertal growth phase. CONCLUSIONS: Dental maturation assessment is only useful for diagnosis of the prepubertal and postpubertal growth phases.

MRI in the assessment of growth arrest.

OBJECTIVE: To compare MRI with X-ray tomography in the assessment of bone bridges across the growth plate. MATERIALS AND METHODS: The investigation consisted of two parts. (1) Eleven children with 13 epiphyses suspected of physeal growth arrests were examined with conventional X-ray tomography and MRI. The bar was post-traumatic in eight children, postinfectious in two and due to a congenital, operated pes equinovarus in one. Three blinded radiologists separately evaluated the examinations retrospectively. (2) The images of four children with known physeal bars in the ankle were mixed with 36 normal examinations obtained 1-year after trauma and evaluated blindly by three radiologists. RESULTS: In 5 of 13 epiphysis, the bony bridge was considered smaller on MRI than on X-ray tomography, in 7 of 13 it was considered equal, while it was larger only in one. The interobserver agreement (weighted kappa) was 0.8 (very good) for MRI, 0.76 (good) for X-ray tomography and 0.60 (moderate) for radiographs. The four bony bridges were easily detected on MRI. CONCLUSIONS: Compared to MRI, the size of bridges was estimated larger by tomography in about half of the patients.

Assessment of an ectopic bone formation system with implantation of pelleted rat primary growth cartilage cells.

To assess the ectopic bone formation system, growth cartilage (GC) cells were implanted to ectopic sites, and the effect of the implanting sites and gender of animals on bone formation were examined. Each 5 x 10(5) batch of GC cells from young rat ribs was pelleted, cultured in calcification medium, and implanted to ectopic sites (in a peritoneal cavitiy or on subcutaneous muscle) in female or male rats. The implanted pellets formed bone after 3-4 weeks at the ectopic sites. Histological examination concluded that, first, a subcutaneous muscle site is more conductive to bone formation than a peritoneal cavity site and, second, the pelleted GC cells implanted in male rats formed bone more effectively than those in female rats. Therefore, at present, the ectopic bone formation system of pelleted primary GC cells onto subcutaneous muscle of male rats is an appropriate system for the evaluation of bone formation.

Radiographic assessment of longitudinal growth of the rabbit femoral physes.

Using surgically implanted metal markers, serial radiographs of 17 immature femurs were evaluated for growth of the entire femur and of the distal femoral physis in rabbits 20 to 100 days of age. From these data the rate of longitudinal growth was plotted. The most rapid growth during the study period was from 20 to 40 days. Growth rates reached a plateau at 100 days of age. The increases in length for unit of time were compared for the entire femur and the distal physis. The distal physis was responsible for approximately 65-70% of the femoral growth for the study period. As an internal control of reproducibility of measurement, two means of determining distal femoral growth rates were compared. Their best fit curves proved to be almost identical. The model of evaluation of femoral growth is reproducible and can serve as a control against which variables in growth can be compared.

Assessment of bony bridge by computed tomography: experimental model in the rabbit and clinical application.

A bony bridge was created in the growth plates of young rabbits. Weekly computed tomography (CT) scanning was done in the axial (transverse) plane for 3 weeks. Transverse histological sections from the plate area were examined after 3 weeks. The CT image showed the exact location and extent of the sclerotic bony bridge. The area of the bony bridge as a percentage of the plate was measured from the CT image. Good correlation was found between the CT image and the histological section. This technique has been applied to children, and three such examples show accurate assessment of the growth plate.