{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:34:12Z","timestamp":1780335252189,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R21CA294634"],"award-info":[{"award-number":["NIH R21CA294634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01EB035092"],"award-info":[{"award-number":["NIH R01EB035092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>For proton FLASH therapy, range\u2010modulating devices are inserted in the beam path to create a spread\u2010out\u2010Bragg\u2010peak (SOBP) for ultrafast delivery using a single energy pencil beam scanning technique. Current design typically consists of uniform density spikes with range modulation achieved by changing the area and height of the spikes, which has limited structural stability and modulation flexibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We present a new class of 3D\u2010printed range\u2010modulating devices for particle therapy with spatially modulated density.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PixelPrint technology (Laboratory for Advanced Computed Tomography Imaging, University of Pennsylvania, PA) was used to 3D\u2010print the variable density range\u2010modulator, by continuously varying the ratio of filament to air in each voxel. With specific thickness and spatial density modulation, SOBP of varying widths can be created. A calibration phantom was 3D printed and scanned by a dual\u2010energy computed tomography (CT) scanner to characterize the physical and radiological properties of the PixelPrint technology. We developed an inverse optimization algorithm to generate the density map for producing SOBP from monoenergetic proton beam and verified by MCsquare (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.openmcsquare.org\/\">http:\/\/www.openmcsquare.org\/<\/jats:ext-link>\n                      ), an open\u2010source Monte Carlo (MC) simulation platform. The range modulation characteristics were measured using a multi\u2010layer ionization chamber (MLIC) under monoenergetic proton field irradiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The proposed optimization framework generated the density distributions for multiple SOBP widths. MC simulation verified the width and flatness of created SOBPs. The CT scan of a 3\u2010cm SOBP modulator showed good fidelity of the desired density distribution, except for the highest density regions. MLIC measurements confirmed the accuracy of the produced SOBP with multiple proton beam energies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A novel variable density range\u2010modulating device for proton therapy was successfully developed. These devices have the potential to be handled easily and significantly speed\u2010up proton therapy treatment delivery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70013","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T03:29:38Z","timestamp":1758598178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Optimization and fabrication of a novel 3D\u2010printed variable density range modulation device for proton FLASH beams"],"prefix":"10.1002","volume":"52","author":[{"given":"Wenbo","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khayrullo","family":"Shoniyozov","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Radiology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Department of Radiology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon\u2010Keng Kevin","family":"Teo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Hospital of the University of Pennsylvania  Philadelphia Pennsylvania 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