{"doi":"10.1101/2025.02.01.636061","title":"Differentiating unirradiated mice from those exposed to conventional or FLASH radiotherapy using MRI","abstract":"Background and purpose: The FLASH effect expands the therapeutic ratio of tumor control to normal tissue toxicity observed after delivery of ultra-high (>100 Gy/s FLASH-RT) vs. conventional dose rate radiation (CONV-RT). In this first exploratory study, we assessed whether ex-vivo Magnetic Resonance Imaging (MRI) could reveal long-term differences after FLASH-RT and CONV-RT whole-brain irradiation. Materials and methods: Female C57BL/6 mice were divided into three groups: control (non-irradiated), conventional (CONV-RT 0.1 Gy/s), and ultra-high dose rates (FLASH-RT 1 pulse, 5.5 × 10^6 Gy/s), and received 10 Gy of whole-brain irradiation in a single fraction at 10 weeks of age. Mice were evaluated by Novel Object Recognition cognitive testing at 10 months post-irradiation and were sampled at 13 months post-irradiation. Ex-vivo brains were imaged with a 14.1 Tesla/26 cm magnet with a multimodal MRI protocol, including T2-weighted TurboRare (T2W) and diffusion-weighted imaging (DWI) sequences. Results: In accordance with previous results, cognitive tests indicated that animals receiving CONV-RT exhibited a decline in cognitive function, while FLASH-RT performed similarly to the controls. MRI showed decreased hippocampal mean intensity in the CONV-RT mice compared to controls but not in the FLASH-RT group. Comparing CONV-RT to control, we found significant changes in multiple whole-brain diffusion metrics, including the mean Apparent Diffusion Coefficient (ADC) and Mean Apparent Propagator (MAP) metrics. By contrast, no significant diffusion changes were found between the FLASH-RT and control groups. In an exploratory analysis compared to controls, regional diffusion metrics were primarily altered in the basal forebrain and the insular cortex after CONV-RT, and after FLASH-RT, a trend reduction was also observed. Conclusion: This study presents initial evidence that MRI can uncover clear changes in the brain after CONV-RT but not after FLASH-RT. The MRI results aligned with the observed cognitive protection after FLASH-RT, indicating the potential use of MRI to analyze the FLASH response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":561660,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.835,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1128725,"name":"Adam Kimbler","orcid":"0000-0001-5885-9596","position":1,"is_corresponding":false},{"id":1426771,"name":"Olivia Drayson","orcid":null,"position":2,"is_corresponding":false},{"id":262951,"name":"Bernard Lanz","orcid":"0000-0001-5136-075X","position":3,"is_corresponding":false},{"id":1426407,"name":"Jessie Mosso","orcid":"0000-0001-6318-9507","position":4,"is_corresponding":false},{"id":656468,"name":"Veljko Grilj","orcid":"0000-0001-6573-8063","position":5,"is_corresponding":false},{"id":232791,"name":"Benoît Petit","orcid":"0009-0003-9397-4583","position":6,"is_corresponding":false},{"id":1037051,"name":"Javier Franco‐Pérez","orcid":"0000-0001-9670-8502","position":7,"is_corresponding":false},{"id":488831,"name":"Aaron B. Simon","orcid":"0000-0003-4685-2711","position":8,"is_corresponding":false},{"id":232800,"name":"Charles L. Limoli","orcid":"0000-0002-1321-4142","position":9,"is_corresponding":false},{"id":232801,"name":"Marie‐Catherine Vozenin","orcid":"0000-0002-2109-8073","position":10,"is_corresponding":false},{"id":1464204,"name":"Craig Stark","orcid":null,"position":11,"is_corresponding":false},{"id":1037050,"name":"Paola Ballesteros‐Zebadúa","orcid":"0000-0003-1263-2163","position":12,"is_corresponding":false},{"id":1170005,"name":"Jeannette Jansen","orcid":"0000-0002-8625-3978","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:56:01.883848Z","pmid":"39974878","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}