Automated volumetric growth plate measurement using magnetic resonance imaging for monitoring skeletal toxicity in children treated on investigational drug trials

Purpose: Targeted anticancer agents have been reported to have side effects on the skeletal system such as thickening of the epiphyseal growth plate in preclinical models of juvenile, but not mature, animals. Careful evaluation of skeletal toxicity in the clinical development of targeted therapies for children is required. We validated a novel method to measure the growth plate volume using MRI. Experimental Design: A semiautomated method of volumetric growth plate measurement was developed on the basis of the differences of pixel intensity of the growth plate from surrounding bone on T ₁ sagittal MRI. Two observers measured the femoral growth plate volume and thickness on three different days using 20 pediatric knee MRIs obtained at the NIH. Five subjects had two knee MRIs obtained on the same day to evaluate intrasubject reproducibility. Results: Volumetric analysis showed low intraobserver variability, with the coefficient of variation for the two observers ranging from 0.2% to 6.1%. Interobserver correlation was 0.99, and good concordance was shown with a mean volume difference of -1.8mm ³. One-dimensional measurements had poorer intra and interobserver consistency. No statistically significant differences in volumetric measurements were observed between the two scans done on the same day in five subjects (P = 0.5). Conclusions: MRI volumetric growth plate measurement is a reproducible and sensitive method to evaluate meaningful growth plate volume changes over time. This tool, along with close monitoring of height and laboratory evaluations for bone metabolism, may be used to evaluate potential bone and growth toxicities of children enrolled in trials of investigational drugs.