X-ray histology on rapidly fixed fresh tumor tissue samples for fast resection margin assessment

Accurate assessment of the resection margin is of key importance for patient outcome after tumor surgery. Intraoperative assessment is preferable but present methods like fresh-frozen sectioning risk sampling errors and provide only 2D information. Classical 2D histology has better quality but is too slow for intraoperative feedback. In the present proof-of-concept study we show that laboratory x-ray histology based on propagation-based phase-contrast microtomography has potential for 3D intraoperative resection margin assessment. Our system includes a liquid-metal-jet high-brightness microfocus source, precision stages and a high-resolution detector, providing fast, high-contrast, near-cellular-resolution 3D imaging. The tissue is prepared by rapid acetone fixation before the 3D x-ray imaging. We demonstrate the method on several tumor types in liver and pancreas, as well as on different sarcomas. After the x-ray histology, classical histology was performed on the same samples for comparison. The two methods compare excellently on the liver and pancreas samples and reasonably on the morphologically more difficult sarcomas. The imaging currently takes 4-5 h with our prototype instrument, and we outline how to go below 1 h for the full procedure. We conclude that 3D x-ray histology can be developed to provide intraoperative resection margin assessment.