Two-dimensional inverse planning and delivery with a preclinical image guided microirradiator

Purpose: Recent advances in preclinical radiotherapy systems have provided the foundation for scaling many of the elements of clinical radiation therapy practice to the dimensions and energy demanded in small animal studies. Such systems support the technical capabilities to accurately deliver highly complex dose distributions, but methods to optimize and deliver such distributions remain in their infancy. This study developed an optimization method based on empirically measured two-dimensional dose kernel measurements to deliver arbitrary planar dose distributions on a recently developed small animal radiotherapy platform. Methods: A two-dimensional dose kernel was measured with repeated radiochromic film measurements for the circular 1 mm diameter fixed collimator of the small animal radiotherapy system at 1 cm depth in a solid water phantom. This kernel was utilized in a sequential quadratic programming optimization framework to determine optimal beam positions and weights to deliver an arbitrary desired dose distribution. The positions and weights were then translated to a set of stage motions to automatically deliver the optimized dose distribution. End-to-end efficacy of the framework was quantified through five repeated deliveries of two dosimetric challenges: (1) a 5 mm radius bullseye distribution, and (2) a "sock" distribution contained within a 9 × 13 mm bounding box incorporating rectangular, semicircular, and exponentially decaying geometric constructs and a rectangular linear dose gradient region. These two challenges were designed to gauge targeting, geometric, and dosimetric fidelity. Results: Optimization of the bullseye and sock distributions required 2.1 and 5.9 min and utilized 50 and 77 individual beams for delivery, respectively. Automated delivery of the resulting optimized distributions, validated using radiochromic film measurements, revealed an average targeting accuracy of 0.32 mm, and a dosimetric delivery error along four line profiles taken through the sock distribution of 3.9%. Mean absolute delivery error across the 0-1 Gy linear dose gradient over 7.5 mm was 0.01 Gy. Conclusions: The work presented here demonstrates the potential for complex dose distributions to be planned and automatically delivered with millimeter scale heterogeneity at submillimeter accuracy. This capability establishes the technical foundation for preclinical validation of biologically guided radiotherapy investigations and development of unique radiobiological experiments.