{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:32:26Z","timestamp":1791484346721,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg within the funding programme \u201cOpen Access Publication Funding\u201d","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (\u00b13) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p \u2264 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p \u2264 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p \u2264 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p &lt; 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p \u2264 0.034).<\/jats:p>","DOI":"10.3390\/brainsci12070879","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:15:05Z","timestamp":1656933305000},"page":"879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of Hippocampal Sparing Radiotherapy on Brain Microstructure\u2014A Diffusion Tensor Imaging Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Johannes G.","family":"Dinkel","sequence":"first","affiliation":[{"name":"Neuroradiologisches Institut des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godehard","family":"Lahmer","sequence":"additional","affiliation":[{"name":"Strahlenklinik des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6795-5627","authenticated-orcid":false,"given":"Angelika","family":"Mennecke","sequence":"additional","affiliation":[{"name":"Neuroradiologisches Institut des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6815-4765","authenticated-orcid":false,"given":"Stefan W.","family":"Hock","sequence":"additional","affiliation":[{"name":"Neuroradiologisches Institut des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5426-8342","authenticated-orcid":false,"given":"Tanja","family":"Richter-Schmidinger","sequence":"additional","affiliation":[{"name":"Psychiatrische und Psychotherapeutische Klinik des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8295-7145","authenticated-orcid":false,"given":"Rainer","family":"Fietkau","sequence":"additional","affiliation":[{"name":"Strahlenklinik des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-3226","authenticated-orcid":false,"given":"Luitpold","family":"Distel","sequence":"additional","affiliation":[{"name":"Strahlenklinik des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-2872","authenticated-orcid":false,"given":"Florian","family":"Putz","sequence":"additional","affiliation":[{"name":"Strahlenklinik des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"D\u00f6rfler","sequence":"additional","affiliation":[{"name":"Neuroradiologisches Institut des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-2582","authenticated-orcid":false,"given":"Manuel A.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Neuroradiologisches Institut des Universit\u00e4tsklinikums Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S236","DOI":"10.4103\/2152-7806.111301","article-title":"Whole brain radiotherapy for brain metastasis","volume":"4","author":"McTyre","year":"2013","journal-title":"Surg. 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