Early in vivo Radiation Damage Quantification for Pediatric Craniospinal Irradiation Using Longitudinal MRI for Intensity Modulated Proton Therapy

Abstract

Proton vertebral body sparing craniospinal irradiation (CSI) treats the thecal sac while avoiding the anterior vertebral bodies in an effort to reduce myelosuppression and growth inhibition. However, robust treatment planning needs to compensate for proton range uncertainty, which contributes unwanted doses within the vertebral bodies. This work aimed to develop an early in vivo radiation damage quantification method using longitudinal magnetic resonance (MR) scans to quantify the dose effect during fractionated CSI. Ten pediatric patients were enrolled in a prospective clinical trial of proton vertebral body sparing CSI, in which they received 23.4 to 36 Gy. Monte Carlo robust planning was used, with spinal clinical target volumes defined as the thecal sac and neural foramina. T1/T2-weighted MR scans were acquired before, during, and after treatments to detect a transition from hematopoietic to less metabolically active fatty marrow. MR signal intensity histograms at each time point were analyzed and fitted by multi-Gaussian models to quantify radiation damage. Fatty marrow filtration was observed in MR images as early as the fifth fraction of treatment. Maximum radiation-induced marrow damage occurred 40 to 50 days from the treatment start, followed by marrow regeneration. The mean damage ratios were 0.23, 0.41, 0.59, and 0.54, corresponding to 10, 20, 40, and 60 days from the treatment start. We demonstrated a noninvasive method for identifying early vertebral marrow damage based on radiation-induced fatty marrow replacement. The proposed method can be potentially used to quantify the quality of CSI vertebral sparing and preserve metabolically active hematopoietic bone marrow.