{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:48:39Z","timestamp":1773330519455,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,9]]},"group-title":"Radiology and Imaging","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Proton beam therapy (PBT) offers a unique potential for dose conformity to tumors while sparing surrounding healthy tissues. Current PBT accuracy, however, is fundamentally limited by range uncertainties from tissue density variations and anatomical changes, yet no clinically viable methods exist for localizing the dose delivery pulse-by-pulse inside patients during pencil beam scanning (PBS). We developed and clinically demonstrated a first-of-its-kind radiation acoustic beam localization (iRABL) system for real-time tracking PBS trajectory and mapping dose deposition deep in patient\u2019s body during PBT. A clinical-grade compact iRABL system featuring high speed, super-resolution, and high sensitivity was specifically designed for PBT applications. Its clinical feasibility was validated through the first-in-human study on prostate cancer patients, demonstrating the capability for\n                  <jats:italic>in vivo<\/jats:italic>\n                  proton dose mapping without interfering with treatment delivery. System performance, including spatial resolution, imaging speed for tracking beam trajectory and temporal dose accumulation, and dosimetric accuracy, was quantitatively characterized using tissue-equivalent phantoms and clinical treatment plans. This iRABL system achieved displacement resolution of 0.1 mm laterally and 0.2 mm axially, exceeding the acoustic diffraction limit by an order of magnitude and surpassing typical proton beam spot sizes. This super-resolution capability, combined with GPU-accelerated image reconstruction and processing, enabled single-pulse detection at a frame rate of 1 kHz, matching the proton system\u2019s pulse repetition rate. Dosimetric validation using clinical M-shaped treatment plans met clinical criteria with gamma index passing rates exceeding 90% at 3 mm\/3% tolerance, confirming high accuracy for mapping delivered dose distributions. For the first time, by leveraging the high sensitivity and the high speed of our newly developed iRABL system, we are able to localize proton beam and map the proton dose deposition during PBS with sub-diffraction-limit spatial resolution, pulse-by-pulse imaging speed, and clinical grade accuracy. This capability, which addresses fundamental limitations in current treatment monitoring, holds promise for advancing PBT toward image-guided \"proton surgery\".\n                <\/jats:p>","DOI":"10.64898\/2026.03.07.26347755","type":"posted-content","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:20:12Z","timestamp":1773098412000},"source":"Crossref","is-referenced-by-count":0,"title":["Ionizing radiation acoustic beam localization: one step towards \"proton surgery\""],"prefix":"10.64898","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Oraiqat","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Moffitt Cancer Center, Tampa, 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Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Dykstra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale","family":"Litzenberg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Cuneo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Mendenhall","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Florida, Gainesville, Florida"},{"name":"University of Florida Health Proton Therapy Institute, Jacksonville, Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Florida, Gainesville, Florida"},{"name":"University of Florida Health Proton Therapy Institute, Jacksonville, Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Jean-Baptiste","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Florida, Gainesville, Florida"},{"name":"University of Florida Health Proton Therapy Institute, Jacksonville, 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