Publications

Background: Accurate and precise methods to predict growth remain lacking. Diffusion tensor imaging (DTI) depicts the columnar structure of the physis and metaphyseal spongiosa and provides measures of tract volume and length that may help predict growth.

Purpose: To validate physeal DTI metrics as predictors of height velocity (1-year height gain from time of MRI examination) and total height gain (height gain from time of MRI examination until growth stops) and compare the prediction accuracy with bone age–based models.

Materials and Methods: Femoral DTI studies (b values = 0 and 600 sec/mm2; directions = 20) of healthy children who underwent MRI of the knee between February 2012 and December 2016 were retrospectively analyzed. Children with height measured at MRI and either 1 year later (height velocity) or after growth cessation (total height gain, mean = 34 months from MRI) were included. Physeal DTI tract volume and length were correlated with height velocity and total height gain. Multilinear regression was used to assess the potential of DTI metrics in the prediction of both parameters. Bland-Altman plots were used to compare root mean square error (RMSE) and bias in height prediction using DTI versus bone age methods.

Results: Eighty-nine children (mean age, 13 years ± 3 [SD]; 47 boys) had height velocity measured, and 70 (mean age, 14 years ± 1; 36 girls) had total height gain measured. Tract volumes correlated with height velocity (r2 = 0.49) and total height gain (r2 = 0.46) (P < .001 for both) after controlling for age and sex. Tract volume was the strongest predictor for height velocity and total height gain. An optimal multilinear model including tract volume improved prediction of height velocity (R2 = 0.63, RMSE = 1.7 cm) and total height gain (R2 = 0.59, RMSE = 1.8 cm) compared with bone age–based methods (height velocity: R2 = 0.32, RMSE = 2.9 cm; total height gain: R2 = 0.42, RMSE = 5.0 cm).

Conclusion: Models using tract volume derived from diffusion tensor imaging may perform better than bone age–based models in children for the prediction of height velocity and total height gain.

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• Background: Current methods to predict height and growth failure are imprecise. MRI measures of physeal cartilage are promising biomarkers for growth.
• Purpose: In the physis, to assess how 3D MRI volume measurements, and diffusion tensor imaging (DTI) measurements (tract volume and length) correlate with growth parameters and detect differences in growth. We compared patients exposed to cis-retinoic acid, which causes physeal damage and growth failure, with normal subjects.
• Study Type: Case–control.
• Population: Twenty pediatric neuroblastoma survivors treated with cis-retinoic acid and 20 age- and sex-matched controls.
• Field Strength/Sequence: 3T; DTI and 3D double-echo steady-state (DESS) sequences.
• Assessment: On distal femoral MR studies, physeal 3D volume and DTI tract measurements were calculated and compared to height.
• Statistical Tests: We used partial Spearman correlation, analysis of covariance, logistic regression, Wald test, and the intraclass correlation coefficient (ICC).
• Results: The height percentile correlated most strongly with DTI tract volumes (r = 0.74), followed by mean tract length (r = 0.53) and 3D volume (r = 0.40) (all P < 0.02). Only tract volumes and lengths correlated with annualized growth velocity. Relative to controls, patients showed smaller tract volumes (8.00 cc vs. 13.71 cc, P < 0.01), shorter tract lengths (5.92 mm vs 6.99 mm, P = 0.03), and smaller ratios of 3D cartilage volume to tract length; but no difference (4.51 cc vs 4.85 cc) in 3D MRI volumes. The 10 patients with the lowest height percentiles had smaller tract volumes (5.07 cc vs. 10.93 cc, P < 0.01), but not significantly different 3D MRI volumes. Tract volume is associated with abnormal growth, with an accuracy of 75%.
• Data Conclusion: DTI tract volume of the physis/metaphysis predicts abnormal growth better than physeal cartilage volumetric measurement and correlates best with height percentile and growth velocity.

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• Background: Diffusion-tensor imaging (DTI) depicts the movement of water through columns of cartilage and newly formed bone and provides information about velocity of growth and growth potential.
• Objective: To determine the correlation between DTI tractography parameters of the distal femoral physis and metaphysis and the height change after DTI in pubertal and post-pubertal children.
• Materials and methods: We retrospectively analyzed DTI images of the knee in 47 children with a mean age of 14.1 years in a 2-year period. In sagittal echoplanar DTI studies, regions of interest were placed in the femoral physis. Tractography was performed using a fractional anisotropy threshold of 0.15 and a maximum turning angle of 40°. The sample was divided to assess short-term and long-term growth after DTI. Short-term growth (n=25) was the height change between height at MRI and 1 year later. Long-term growth (n=36) was the height gain between height at MRI and at the growth plateau.
• Results: For the short-term group, subjects with larger tract volume (R2=0.40) and longer track lengths (R2=0.38) had larger height gains (P<0.01). For the long-term group, subjects with larger tract volume (R2=0.43) and longer track lengths (R2=0.32) had a larger height gain at the growth plateau (P<0.01). Intra- and inter-observer variability were good-excellent.
• Conclusion: Follow-up data of growth 1 year after DTI evaluation and at skeletal maturity confirms that DTI parameters are associated with the amount of post-imaging growth.

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• Background: The survival of patients with high-risk neuroblastoma has increased with multimodal therapy, but most survivors demonstrate growth failure.
• Objective: To assess physeal abnormalities in children with high-risk neuroblastoma in comparison to normal controls by using diffusion tensor imaging (DTI) of the distal femoral physis and adjacent metaphysis.
• Materials and methods: We prospectively obtained physeal DTI at 3.0 T in 20 subjects (mean age: 12.4 years, 7 females) with high-risk neuroblastoma treated with high-dose cis-retinoic acid, and 20 age- and gender-matched controls. We compared fractional anisotropy (FA), normalized tract volume (cm3/cm2) and tract concentration (tracts/cm2) between the groups, in relation to height Z-score and response to growth hormone therapy. Tractography images were evaluated qualitatively.
• Results: DTI parameters were significantly lower in high-risk neuroblastoma survivors compared to controls (P<0.01), particularly if the patients were exposed to both cis-retinoic acid and total body irradiation (P<0.05). For survivors and controls, DTI values were respectively [mean ± standard deviation]: tract concentration (tracts/cm2), 23.2±14.7 and 36.7±10.5; normalized tract volume (cm3/cm2), 0.44±0.27 and 0.70±0.21, and FA, 0.22±0.05 and 0.26±0.02. High-risk neuroblastoma survivors responding to growth hormone compared to non-responders had higher FA (0.25±0.04 and 0.18±0.03, respectively, P=0.02), and tract concentration (tracts/cm2) (31.4±13.7 and 14.8±7.9, respectively, P<0.05). FA, normalized tract volume and tract concentration were linearly related to height Z-score (R2>0.31; P<0.001). Qualitatively, tracts were nearly absent in all non-responders to growth hormone and abundant in all responders (P=0.02).
• Conclusion: DTI shows physeal abnormalities that correlate with short stature in high-risk neuroblastoma survivors and demonstrates response to growth hormone treatment.

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• Purpose: To determine the changes of diffusion-tensor imaging (DTI) and tractography in the distal femur and proximal tibia related to age, sex, and height.
• Materials and Methods: Following institutional review board approval, with waiver of consent and with HIPAA compliance, the authors retrospectively analyzed DTI images of the knee in 151 children, 73 girls (median age, 14.1 years; range, 6.5–17.8 years) and 78 boys (median age, 16.6 years; range, 6.9–17.9 years), studied from January 2013 to October 2014. At sagittal echo-planar DTI (20 directions, b values of 0 and 600 sec/mm2), regions of interest were placed in the tibial and femoral physes. Using a fractional anisotropy threshold of 0.15 and an angle threshold of 40°, the authors performed tractography and measured apparent diffusion coefficient (ADC) and tract length and volume. Changes related to age, sex, and height were evaluated by using fitted nonlinear polynomial functions on bootstrapped samples.
• Results: Femoral tract volume and length increased and then decreased with age (P < .001); the peaks of femoral tract volume are consistent with the growth spurt, occurring earlier in girls (10.8 years) than in boys (13.0 years) (P < .001). Girls had smaller tract volumes in comparison to boys (P = .013). ADC peaks 2 years earlier than tract volume (girls at 9.3 years, boys at 11.0 years). Girls with greater than 50th percentile of height had longer tracts and greater tract volumes compared with girls with less than 50th percentile (P < .020). DTI parameters of boys do not correlate with percentile of height (P > .300).
• Conclusion: DTI of the physis and metaphysis shows greater tract length and volumes in subjects who are at ages when the growth is fastest. ADC and tract length and volume have an earlier and smaller peak in girls than in boys. Femoral tract length and volume are larger in taller girls.

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• Purpose: To determine the feasibility of using in vivo diffusion-tensor imaging and tractography of the physis to examine changes related to rate of growth, location, and age.
• Materials and methods: This retrospective study was institutional review board approved and HIPAA compliant and the requirement for informed consent was waived. Diffusion-tensor imaging of the knee was performed at 3.0 T in 31 subjects (nine boys and 22 girls) with a median age of 13.6 years. The mean ages of boys and girls were 14.7 years (range, 12.0-18.3 years) and 13.2 years (range, 7.0-18.6 years), respectively. Regions of interest were placed in the physis of the tibia and femur, and in the epiphyseal and articular cartilage of these bones. Tractography was performed by using a fractional anisotropic threshold of 0.15 and an angle threshold of 40°. The tractographic patterns were qualitatively evaluated and changes related to age were described. The tract-based apparent diffusion coefficient, fractional anistropy, tensor eigenvalues, and tract length were measured. Diffusion parameters were compared between the center and periphery of the physis, and between the distal femur and proximal tibia.
• Results: Tractography resulted in parallel tracts in the physis and the adjacent metaphysis. Tractographic pattern changed with age, with individuals approaching physeal closure having shorter tracts in a random arrangement. Patterns of tractography varied with age in the femur (P < .001) and tibia (P < .001). Femoral tracts (median length, 6.5 mm) were longer than tibial tracts (median length, 4.3 mm) (P < .001). Tracts in the periphery of the physes were longer than those in the center (femur, P = .005; tibia, P = .004). In the physis of the femur and tibia, a significant age-related decrease was observed in apparent diffusion coefficient (P < .001 for both), axial diffusion (femur, P = .001; tibia, P < .001), and transverse diffusion [P < .001 for both]), and an age-related increase was seen in fractional anistropy (P < .001, for both).
• Conclusion: Diffusion-tensor imaging shows the columnar microstructure of the physis and adjacent metaphysis, and provides further insight into normal growth.

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Diffusion-weighted imaging (DWI) is a powerful tool that has recently been applied to evaluate several pediatric musculoskeletal disorders. DWI probes abnormalities of tissue structure by detecting microscopic changes in water mobility that develop when disease alters the organization of normal tissue. DWI provides tissue characterization at a cellular level beyond what is available with other imaging techniques, and can sometimes identify pathology before gross anatomic alterations manifest. These features of early detection and tissue characterization make DWI particularly appealing for probing diseases that affect the musculoskeletal system. This article focuses on the current and future applications of DWI in the musculoskeletal system, with particular attention paid to pediatric disorders. Although most of the applications are experimental, we have emphasized the current state of knowledge and the main research questions that need to be investigated. Full text

• PURPOSE: To evaluate normal diffusion characteristics in the femur in piglets and changes in diffusion with increasing duration of femoral head ischemia.
• MATERIALS AND METHODS: Normal epiphyses, physes, and metaphyses of piglets were evaluated with line-scan diffusion imaging (n = 12) and diffusion-tensor imaging (n = 4). Apparent diffusion coefficient (ADC) differences between normal proximal and distal femoral structures, epiphyseal and physeal cartilage, and epiphyseal and metaphyseal marrow were compared (Mann-Whitney test). Short-term femoral ischemia was investigated after maximal abduction of the hips for 3 hours (n = 6); ADCs before and after abduction were compared (Wilcoxon signed rank test). Prolonged ischemia was investigated with placement of a ligature around the neck of a femur (n = 7); the ADC of the femur in this condition was compared (Wilcoxon signed rank test) with that of the normal contralateral femur. Changes in ADC ratios at three durations of ischemia (Kruskal-Wallis test) were compared.
• RESULTS: ADC was greater in epiphyseal cartilage (mean ± 1 SD, 1.62 × 10−3 mm2/sec ± 0.38) than it was in physeal cartilage (1.28 × 10−3 mm2/sec ± 0.31) (P < .007) and greater in epiphyseal marrow (1.26 × 10−3 mm2/sec ± 0.38) than it was in metaphyseal marrow (0.91 × 10−3 mm2/sec ± 0.35) (P < .001). There was columnar arrangement of tensors in the physis. ADC decreased 26% after 3 hours of maximal abduction. After femoral neck ligature, ADC increased a mean of 27% after 6 hours and a mean of 75% after 96 hours.
• CONCLUSION: Normal line-scan diffusion imaging findings indicate relative restriction of diffusion in the metaphysis and parallel orientation of tensors in the physis. Diffusion is initially restricted with decreased blood flow but increases if ischemia lasts longer.

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