{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:51:57Z","timestamp":1792590717610,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"13","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"European Fund for Regional Development"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Transarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 (<jats:sup>166<\/jats:sup>Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing <jats:sup>166<\/jats:sup>Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Six patients were treated with <jats:sup>166<\/jats:sup>Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, <jats:sup>166<\/jats:sup>Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for <jats:sup>166<\/jats:sup>Ho TARE.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Administration of <jats:sup>166<\/jats:sup>Ho microspheres within the MRI scanner was feasible in 9\/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18\/19 (95%) of treated tumours. Two CTCAE grade 3\u20134 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4\/18 tumours exhibited signs of saturation, while in 14\/18 tumours, the microsphere uptake patterns did not deviate from the linear trend.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Registration<\/jats:title>\n                <jats:p>Clinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-022-05902-w","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T10:03:43Z","timestamp":1657706623000},"page":"4705-4715","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-6664","authenticated-orcid":false,"given":"Joey","family":"Roosen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-6616","authenticated-orcid":false,"given":"Lovisa E. L.","family":"Westlund Gotby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2402-7617","authenticated-orcid":false,"given":"Mark J.","family":"Arntz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-2879","authenticated-orcid":false,"given":"Jurgen J.","family":"F\u00fctterer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel J. R.","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-8500","authenticated-orcid":false,"given":"Mark W.","family":"Konijnenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4626-6694","authenticated-orcid":false,"given":"Meike W. M.","family":"van Wijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-4357","authenticated-orcid":false,"given":"Christiaan G.","family":"Overduin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-2253","authenticated-orcid":false,"given":"J. Frank W.","family":"Nijsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"issue":"12","key":"5902_CR1","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1016\/S1470-2045(17)30683-6","volume":"18","author":"V Vilgrain","year":"2017","unstructured":"Vilgrain V, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18(12):1624\u201336.","journal-title":"Lancet Oncol"},{"issue":"3","key":"5902_CR2","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00270-018-2133-7","volume":"42","author":"CG Radosa","year":"2019","unstructured":"Radosa CG, et al. Holmium-166 radioembolization in hepatocellular carcinoma: feasibility and safety of a new treatment option in clinical practice. Cardiovasc Intervent Radiol. 2019;42(3):405\u201312.","journal-title":"Cardiovasc Intervent Radiol"},{"issue":"9","key":"5902_CR3","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/S1470-2045(17)30457-6","volume":"18","author":"HS Wasan","year":"2017","unstructured":"Wasan HS, et al. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017;18(9):1159\u201371.","journal-title":"Lancet Oncol"},{"issue":"4","key":"5902_CR4","doi-asserted-by":"publisher","first-page":"582","DOI":"10.2967\/jnumed.117.197194","volume":"59","author":"JF Prince","year":"2018","unstructured":"Prince JF, et al. Efficacy of radioembolization with (166)Ho-microspheres in salvage patients with liver metastases: a phase 2 study. J Nucl Med. 2018;59(4):582\u20138.","journal-title":"J Nucl Med"},{"key":"5902_CR5","doi-asserted-by":"publisher","unstructured":"van Roekel C, et al. Dose-effect relationships of holmium-166 radioembolization in colorectal cancer. J Nucl Med. 2021;62(2):272\u20139.\u00a0https:\/\/doi.org\/10.2967\/jnumed.120.243832.","DOI":"10.2967\/jnumed.120.243832"},{"issue":"5","key":"5902_CR6","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1007\/s00270-017-1871-2","volume":"41","author":"P Reimer","year":"2018","unstructured":"Reimer P, et al. Prognostic factors in overall survival of patients with unresectable intrahepatic cholangiocarcinoma treated by means of yttrium-90 radioembolization: results in therapy-naive patients. Cardiovasc Intervent Radiol. 2018;41(5):744\u201352.","journal-title":"Cardiovasc Intervent Radiol"},{"issue":"9","key":"5902_CR7","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.jvir.2016.05.028","volume":"27","author":"CC Pieper","year":"2016","unstructured":"Pieper CC, et al. Yttrium-90 radioembolization of advanced, unresectable breast cancer liver metastases-a single-center experience. J Vasc Interv Radiol. 2016;27(9):1305\u201315.","journal-title":"J Vasc Interv Radiol"},{"issue":"5","key":"5902_CR8","first-page":"969","volume":"30","author":"C Breedis","year":"1954","unstructured":"Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30(5):969\u201377.","journal-title":"Am J Pathol"},{"key":"5902_CR9","doi-asserted-by":"publisher","unstructured":"Roosen J, et al. To 1000\u00a0Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer. Eur J Nucl Med Mol Imaging.\u00a02021;48(12):3776\u201390.\u00a0https:\/\/doi.org\/10.1007\/s00259-021-05340-0.","DOI":"10.1007\/s00259-021-05340-0"},{"key":"5902_CR10","doi-asserted-by":"publisher","unstructured":"Hermann AL, et al. Relationship of tumor radiation-absorbed dose to survival and response in hepatocellular carcinoma treated with transarterial radioembolization with (90)Y in the SARAH Study. Radiology.\u00a02020;296(3):673\u201384.\u00a0https:\/\/doi.org\/10.1148\/radiol.2020191606.","DOI":"10.1148\/radiol.2020191606"},{"key":"5902_CR11","doi-asserted-by":"publisher","unstructured":"Garin E, et al. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol.\u00a02021;6(1):17\u201329.\u00a0https:\/\/doi.org\/10.1016\/S2468-1253(20)30290-9.","DOI":"10.1016\/S2468-1253(20)30290-9"},{"issue":"12","key":"5902_CR12","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.2967\/jnumed.113.119768","volume":"54","author":"ML Smits","year":"2013","unstructured":"Smits ML, et al. In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies. J Nucl Med. 2013;54(12):2093\u2013100.","journal-title":"J Nucl Med"},{"issue":"3","key":"5902_CR13","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00330-012-2648-2","volume":"23","author":"GH van de Maat","year":"2013","unstructured":"van de Maat GH, et al. MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation. Eur Radiol. 2013;23(3):827\u201335.","journal-title":"Eur Radiol"},{"issue":"10","key":"5902_CR14","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/S1470-2045(12)70334-0","volume":"13","author":"ML Smits","year":"2012","unstructured":"Smits ML, et al. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012;13(10):1025\u201334.","journal-title":"Lancet Oncol"},{"issue":"21","key":"5902_CR15","doi-asserted-by":"publisher","first-page":"5462","DOI":"10.3390\/cancers13215462","volume":"13","author":"J Roosen","year":"2021","unstructured":"Roosen J, et al. Development of an MRI-guided approach to selective internal radiation therapy using holmium-166 microspheres. Cancers. 2021;13(21):5462.","journal-title":"Cancers"},{"key":"5902_CR16","doi-asserted-by":"publisher","unstructured":"Smits MLJ, et al. The superior predictive value of (166)Ho-scout compared with (99m)Tc-macroaggregated albumin prior to (166)Ho-microspheres radioembolization in patients with liver metastases. Eur J Nucl Med Mol Imaging.\u00a02020;47(4):798\u2013806.\u00a0https:\/\/doi.org\/10.1007\/s00259-019-04460-y.","DOI":"10.1007\/s00259-019-04460-y"},{"issue":"2","key":"5902_CR17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 11). Eur J Cancer. 2009;45(2):228\u201347.","journal-title":"Eur J Cancer"},{"key":"5902_CR18","doi-asserted-by":"publisher","unstructured":"Peters SMB, et al. Intra-therapeutic dosimetry of [(177)Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome. Eur J Nucl Med Mol Imaging.\u00a02022;49(2):460\u20139.\u00a0https:\/\/doi.org\/10.1007\/s00259-021-05471-4.","DOI":"10.1007\/s00259-021-05471-4"},{"issue":"3","key":"5902_CR19","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1007\/s00259-018-4209-7","volume":"46","author":"M Del Prete","year":"2019","unstructured":"Del Prete M, et al. Personalized (177)Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial. Eur J Nucl Med Mol Imaging. 2019;46(3):728\u201342.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"8","key":"5902_CR20","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1007\/s00259-019-04340-5","volume":"46","author":"R Salem","year":"2019","unstructured":"Salem R, et al. Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging. 2019;46(8):1695\u2013704.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"5902_CR21","doi-asserted-by":"publisher","unstructured":"Levillain H, et al. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging.\u00a02021;48(5):1570\u201384.\u00a0https:\/\/doi.org\/10.1007\/s00259-020-05163-5.","DOI":"10.1007\/s00259-020-05163-5"},{"issue":"7","key":"5902_CR22","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1007\/s00259-008-0747-8","volume":"35","author":"MA Vente","year":"2008","unstructured":"Vente MA, et al. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs. Eur J Nucl Med Mol Imaging. 2008;35(7):1259\u201371.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"5902_CR23","unstructured":"HEPAR Primary: Holmium-166-radioembolization in hepatocellular carcinoma patients; ClinicalTrials.gov Identifier: NCT03379844; https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03379844."},{"key":"5902_CR24","doi-asserted-by":"publisher","unstructured":"Reinders MTM, et al. Safety and efficacy of holmium-166 radioembolization in hepatocellular carcinoma - the HEPAR Primary study. J Nucl Med.\u00a02022.\u00a0https:\/\/doi.org\/10.2967\/jnumed.122.263823.","DOI":"10.2967\/jnumed.122.263823"},{"issue":"1","key":"5902_CR25","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00330-020-07092-1","volume":"31","author":"R Gutjahr","year":"2021","unstructured":"Gutjahr R, et al. Quantitative dual-energy CT material decomposition of holmium microspheres: local concentration determination evaluated in phantoms and a rabbit tumor model. Eur Radiol. 2021;31(1):139\u201348.","journal-title":"Eur Radiol"},{"issue":"1","key":"5902_CR26","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s41747-020-00157-2","volume":"4","author":"RC Bakker","year":"2020","unstructured":"Bakker RC, et al. Feasibility of CT quantification of intratumoural (166)Ho-microspheres. Eur Radiol Exp. 2020;4(1):29.","journal-title":"Eur Radiol Exp"},{"issue":"3","key":"5902_CR27","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1097\/MNM.0000000000000792","volume":"39","author":"RC Bakker","year":"2018","unstructured":"Bakker RC, et al. Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma: preliminary results of first use. Nucl Med Commun. 2018;39(3):213\u201321.","journal-title":"Nucl Med Commun"},{"issue":"2","key":"5902_CR28","doi-asserted-by":"publisher","first-page":"192","DOI":"10.15403\/jgld-3478","volume":"30","author":"L Bonne","year":"2021","unstructured":"Bonne L, et al. Holmium-166 microspheres are visible in target liver lesions on unenhanced computed tomography. J Gastrointestin Liver Dis. 2021;30(2):192.","journal-title":"J Gastrointestin Liver Dis"},{"key":"5902_CR29","doi-asserted-by":"publisher","first-page":"110244","DOI":"10.1016\/j.msec.2019.110244","volume":"106","author":"AG Arranja","year":"2020","unstructured":"Arranja AG, et al. Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy. Mater Sci Eng C Mater Biol Appl. 2020;106:110244.","journal-title":"Mater Sci Eng C Mater Biol Appl"},{"issue":"1","key":"5902_CR30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ijpharm.2018.06.036","volume":"548","author":"AG Arranja","year":"2018","unstructured":"Arranja AG, et al. Radioactive holmium phosphate microspheres for cancer treatment. Int J Pharm. 2018;548(1):73\u201381.","journal-title":"Int J Pharm"},{"issue":"2","key":"5902_CR31","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.ijrobp.2018.05.062","volume":"102","author":"SC Kappadath","year":"2018","unstructured":"Kappadath SC, et al. Hepatocellular carcinoma tumor dose response after (90)Y-radioembolization with glass microspheres using (90)Y-SPECT\/CT-based voxel dosimetry. Int J Radiat Oncol Biol Phys. 2018;102(2):451\u201361.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"12","key":"5902_CR32","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1007\/s00259-018-4064-6","volume":"45","author":"CL Ho","year":"2018","unstructured":"Ho CL, et al. Radioembolization with (90)Y glass microspheres for hepatocellular carcinoma: significance of pretreatment (11)C-acetate and (18)F-FDG PET\/CT and posttreatment (90)Y PET\/CT in individualized dose prescription. Eur J Nucl Med Mol Imaging. 2018;45(12):2110\u201321.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"5902_CR33","doi-asserted-by":"publisher","unstructured":"Henry EC, et al. Precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model.\u00a0EJNMMI Phys. 2022;9(1):21.\u00a0https:\/\/doi.org\/10.1186\/s40658-022-00447-1.","DOI":"10.1186\/s40658-022-00447-1"},{"issue":"3","key":"5902_CR34","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1177\/1526602821996719","volume":"28","author":"R Drescher","year":"2021","unstructured":"Drescher R, et al. Radioembolization with holmium-166 polylactic acid microspheres: distribution of residual activity in the delivery set and outflow dynamics during planning and treatment procedures. J Endovasc Ther. 2021;28(3):452\u201362.","journal-title":"J Endovasc Ther"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-022-05902-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-022-05902-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-022-05902-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T04:09:11Z","timestamp":1666757351000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-022-05902-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":34,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["5902"],"URL":"https:\/\/doi.org\/10.1007\/s00259-022-05902-w","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]},"assertion":[{"value":"9 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"J. F. W. Nijsen is a co-founder of Quirem Medical which has been acquired by Terumo Europe NV in July 2020. Nijsen has a scientific advisory role and is entitled to certain milestone payments from Terumo which are related to Quirem\u2019s financial, operational and regulatory performance in the future. Furthermore, Nijsen is an inventor on the patents related to radioactive microspheres that are assigned to University Medical Center Utrecht Holding BV, Quirem Medical or BASF Corp. The activities of J. F. W. Nijsen within Quirem Medical are approved and supported by the Board of Directors of the Radboudumc. The other authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}