Radiotherapy beam tracking by dual-modality injectable fiducial marker for X-ray CT and Cherenkov luminescence imaging.

Accurate beam targeting is critical in radiation therapy, particularly for stereotactic treatments of mobile organs where fiducial markers are routinely used for image guidance. However, current approaches do not provide real-time confirmation that the therapeutic radiation beam is accurately delivered to the intended target during irradiation. This study presents a preliminary proof-of-concept evaluation of a dual-modality fiducial marker that combines a liquid injectable fiducial material for X-ray computed tomography (CT) contrast with a biocompatible radioluminescent ink, enabling both pre-treatment localization and intra-treatment optical verification. The proposed formulation can be delivered by syringe into anatomical sites and readily visualized on CT for treatment planning and alignment. During irradiation, Cherenkov light generated within tissue excites the marker, producing visible luminescence detectable with a time-gated imaging system and enabling Cherenkov-excited luminescence imaging (CELI) of beam position in real time. Phantom studies demonstrated detection sensitivity for injected volumes as small as 20 µL and radiation doses as low as 2.8 cGy, with measurable signals at depths up to 8 mm in tissue-mimicking media. The liquid fiducial provided clear CT visualization of the injection site prior to treatment, while CELI enabled real-time visualization of the radiation beam during irradiation in vivo. A strong spatial correlation was observed between emitted luminescence and radiation beam location. These results demonstrate the feasibility of a simple subcutaneous injectable fiducial marker system for real-time beam verification in radiation therapy using clinically Cherenkov imaging cameras.