Two-dimensional inverse planning and delivery for precision preclinical radiobiological investigations

Advances in preclinical radiotherapy systems have provided the technical foundations for delivering highly heterogeneous dose distributions for unique radiobiological experiments, but methods to deliver arbitrary dose distributions are in their infancy. This study developed a method to optimize and automatically deliver planar dose distributions on a recently developed preclinical radiotherapy platform. The method was based on empirically determined dose kernel distributions from radiochromic film measurements. These kernels were used to determine optimal animal stage positions and beam weights to deliver a desired dose distribution at a given depth using a sequential quadratic programming optimization algorithm. The method was validated by end-to-end delivery of two dosimetric challenges designed to quantify targeting and dosimetric accuracy. The results revelead an overall targeting accuracy of 112 μm and a dosimetric delivery error, calculated along four line profiles in radiochromic film measurements, of 6.8%. Mean absolute delivery error across a linear dose gradient between 0 and 1 Gy over 7.5 mm was 0.03 Gy. These results confirm the optimization framework is an effective platform for delivery of millimetre scale heterogeneous dose distributions with sub-millimetre accuracy.