Purpose:Photoacoustic‐ultrasonic (PAUS) imaging, which utilizes an ultrasound transducer to provide co‐registered photoacoustic and pulse‐echo ultrasound images, is capable of measuring temperature non‐invasively while simultaneously providing anatomical images. The sub‐millimeter resolution and centimeter‐order penetration depths achievable with PAUS imaging have the potential to deliver active monitoring of both a targeted tumor microenvironment and nearby healthy tissue during thermal ablation. These characteristics make PAUS imaging a promising new technique for guidance and monitoring during photothermal ablations of solid tumors. In order to assess the potential clinical role of PAUS imaging, the technique was validated against the clinically accepted magnetic resonance thermal imaging approach (MRTI).Methods:To facilitate co‐registration between modalities, the phantom had inclusions of gold nanoshells encapsulating super‐paramagnetic iron oxide (SPIO) particles, where gold enhances the PA signal and SPIOs provide negative contrast on MRI. Several phantom designs were assessed for resilience to heating. PA images were acquired on a Vevo LAZR (FUJIFILM VisualSonics Inc., Toronto, Ontario) PAultrasound small‐animal imaging system (21MHz) operating at 710nm. MRTI experiments were performed using a 6‐channel flex coil (GE Healthcare, Waukesha, WI) on a 3T MRI scanner (Discovery MR750, GE Healthcare, Waukesha, WI) using a fast multi gradient echo acquisition (16 echoes, 128×128 acquisition matrix, 25.6×25.6cm field of view, 3mm slice thickness, 60ms TR, 20° flip angle, 2.9ms minimum TE and 1.6ms echo spacing). The accuracy and spatio‐temporal resolution of PA thermography was cross‐validated with both MRTI and a fluoroptic temperature sensor (LumaSense Technologies, Santa Clara, CA) in the custom‐designed phantom.Results:A thermally stable, dual‐modality phantom was created for cross‐validation of photoacoustic thermography and MRTI. Axial and lateral resolutions of PA images were sub‐millimeter with a temporal resolution of 0.2s, which will accommodate precise real‐time guidance and monitoring.Conclusion:These results indicate that a PA thermography technique offers tremendous promise for real‐time thermal monitoring of ablative therapy.Funding support provided by Cancer Prevention Research Institute of Texas and Julia Jones Matthews family. No disclosures or conflicts of interest.