{"doi":"10.1038/s41598-021-86505-7","title":"Free-water diffusion tensor imaging improves the accuracy and sensitivity of white matter analysis in Alzheimer’s disease","abstract":"Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer's disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer's disease.","journal":"Scientific Reports","year":2021,"id":148544,"datarank":0.7278045395879427,"base_score":4.852030263919617,"endowment":4.852030263919617,"self_citation_contribution":0.7278045395879427,"citation_network_contribution":0.0,"self_endowment_contribution":0.7278045395879427,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":127,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":633468,"name":"Ryan R. Walsh","orcid":null,"position":1,"is_corresponding":false},{"id":477665,"name":"Ashley M. Stokes","orcid":"0000-0003-1137-5003","position":2,"is_corresponding":false},{"id":632192,"name":"Maurizio Bergamino","orcid":"0000-0001-6618-3784","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:46.224799Z","pmid":"33772083","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":[]}