Novel 4π noncoplanar small animal irradiation with rectangular aperture based optimization

Background.Preclinical small-animal studies are essential for understanding radiation-induced biological responses and toxicities, ultimately facilitating translation to clinical interventions. However, the promise is hampered by poor dose conformity achieved in small-animal experiments. The gap has been partially closed with recent advances in image guidance and radiation intensity modulation. The vast differences in the sizes between the small animals and humans, however, demand steeper dose gradient to mimic clinical targeting specificity.Objective.Here, we explore the non-coplanar solution space enabled by the Small Animal Radiation Research Platform (SARRP) to enhance dose delivery specificity.Approach.This study integrates a 4πnon-coplanar beam orientation optimization framework with 4πrectangular apertures-based beam orientation optimization (4π-RABOO) for automated small-animal intensity-modulated radiotherapy (IMRT) planning.Methods.4π-RABOO objective function included anL₂-norm term for dose fidelity, anL₁-norm term for aperture sparsity, and anL_2,1/2group sparsity term for beam selection. Solving the large-scale computational problem was accelerated by replacing the Kronecker product with smaller matrix multiplications and by applying the Fast Iterative Shrinkage Thresholding Algorithm. Three preclinical sites (brain, liver tumor, spine) involving five mice were evaluated against two reference coplanar plans: 5-field rectangular aperture plans and fixed-size aperture plans. Plan evaluation metrics included D2, D98, homogeneity index,R₅₀for planning target volumes, and mean/max doses to organs at risk (OARs).Main Results.4π-RABOO improved plan quality by reducing D2 by up to 17.4%, increasing D98 by up to 17.1%, and loweringR₅₀by over 30% compared to baseline plans. In spine cases, mean doses to critical OARs (bowel, liver, spleen) were reduced by up to 64.5%, 51.6%, and 93.1%, respectively. The enhanced dosimetric performance came at the cost of increased plan complexity, with 2-3X more apertures per case.Significance.Integrating beam orientation and rectangular aperture optimization into small-animal IMRT on the SARRP generates dosimetrically superior plans, significantly improving target dose homogeneity and adjacent tissue sparing.