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Herein, an offline programming guidance (OLPG) scheme for aggregated MNPs is proposed based on a real\u2010time aggregation volume estimator. The proposed aggregation volume estimator based on a magnetic drug\u2010targeting simulator reflects volume changes of aggregated MNPs; hence, it can model a magnetic force acting on aggregated MNPs in real time while enhancing targeting performance. The proposed guidance system is evaluated using a simulation testbed and in\u2009vitro model of the rat brain, which yields comparable results at different fluid viscosities, flow velocities, target areas, and flow types. The OLPG with the aggregation volume estimator improves targeting performance by 116%\u2013409% compared with the default mode, and by 111%\u2013180% compared to the performance without the aggregation volume estimator. Furthermore, a guidance margin predicts enhanced targeting performance (root\u2010mean\u2010square error\u2009&lt;\u20095%) irrespective of the flow environment. The proposed guidance strategy has the potential to overcome the problems caused by the lack of an imaging modality, control\u2010system complexity, and low targeting performance.<\/jats:p>","DOI":"10.1002\/aisy.202300128","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T21:24:31Z","timestamp":1688073871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aggregation Volume Estimator\u2013Based Offline Programming Guidance of Magnetic Nanoparticles in the Realistic Rat\u2010Brain Vasculature Model"],"prefix":"10.1002","volume":"5","author":[{"given":"Myungjin","family":"Park","sequence":"first","affiliation":[{"name":"School of Integrated Technology Gwangju Institute of Science and Technology Institute of Integrated Technology  123 Cheomdan Gwagiro Gwangju 61005 Republic of Korea"}]},{"given":"Seungjun","family":"Oh","sequence":"additional","affiliation":[{"name":"School of Integrated Technology Gwangju Institute of Science and Technology Institute of Integrated Technology  123 Cheomdan Gwagiro Gwangju 61005 Republic of Korea"}]},{"given":"Tuan","family":"Anh Le","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic Scottsdale  13400 E Shea Blvd Scottsdale AZ 85259 USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1350-5334","authenticated-orcid":false,"given":"Jungwon","family":"Yoon","sequence":"additional","affiliation":[{"name":"School of Integrated Technology Gwangju Institute of Science and Technology Institute of Integrated Technology  123 Cheomdan Gwagiro Gwangju 61005 Republic of Korea"}]}],"member":"311","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2008.12.004"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-010510-103409"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scirobotics.aba5726"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7NR00772H"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781420004656"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(98)00027-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11051-014-2734-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c07753"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/aisy.202100116"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-020-00275-x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.03.031"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12070665"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmmm.2016.11.016"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmmm.2022.170110"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-019-02317-x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2012.2213340"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe5914"},{"journal-title":"IEEE Trans. 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