Evaluating growth failure with diffusion tensor imaging in pediatric survivors of high-risk neuroblastoma treated with high-dose cis-retinoic acid

Pediatr Radiol. 2019 Jul;49(8):1056-1065. doi: 10.1007/s00247-019-04409-1. Epub 2019 May 4.


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.

Keywords: Children; Cis-retinoic acid; Diffusion tensor imaging; Growth; High-risk neuroblastoma; Magnetic resonance imaging; Physis.

MeSH terms

  • Adolescent
  • Age Factors
  • Anisotropy
  • Body Height / drug effects
  • Case-Control Studies
  • Child
  • Diffusion Tensor Imaging / methods*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Femur / diagnostic imaging
  • Femur / pathology
  • Growth Disorders / drug therapy*
  • Growth Disorders / etiology
  • Humans
  • Linear Models
  • Male
  • Multivariate Analysis
  • Neuroblastoma / diagnostic imaging*
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / mortality
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Survivors
  • Tretinoin / adverse effects
  • Tretinoin / therapeutic use*


  • Tretinoin