Commissioning of a multislit collimator system for experimental pMBRT studies with uniform target dose.

. Proton minibeam radiotherapy (pMBRT) is a novel approach to widen the therapeutic window by balancing tumor control and reducing toxicity to healthy tissues. Among the various ways to generate minibeams, a multislit collimator (MSC) is a convenient approach for integration into existing beamlines. Here, we focus on optimizing the MSC to achieve uniform doses in the planning target volume (PTV), enabling direct comparisons with conventional proton therapy and highlighting pMBRT's potential clinical benefits.. This study details the design, development, and commissioning of an MSC system for experimental pMBRT, using Geant4 simulations for collimator optimization and experimental validation with radiochromic film, a diamond detector, and a plane-parallel ionization chamber. The optimization process focused on collimator parameters such as material, thickness, center-to-center distance (CTC), and geometric throughput, tailored for a murinereference setup. Treatment plans were modified to ensure uniform PTV doses, compensating the effect of MSCs. Simulations emphasize on accurate collimator optimization to ensure the maximum dose contrast between peaks and valleys at the entrance while retaining uniform PTV dose.. Although tungsten MSCs can produce sharp dose contrasts in normal tissue, our experimental findings suggest brass as the preferred material to reduce activation, particularly important for repeated high-dose irradiations. We found that a 50 mm thickness, 2 mm CTC distance, and 50% throughput were optimal for our reference treatment plan (84 to 107 MeV). With a sufficiently uniform PTV dose, we experimentally obtained a valley-to-peak dose ratio of 0.13. The dose pattern is highly sensitive to MSC alignment, although phase shifts have minimal impact.. The non-parallel nature of pencil beam scanning underscores the importance of precise MSC alignment to preserve uniform target dose and high dose contrast at the entrance. Our optimized configurations, experimentally validated, offer a foundation for preclinical and clinical pMBRT collimator construction.