{"doi":"10.1002/jmri.70118","title":"Unchanged Early Diffusion Tensor Imaging Along Perivascular Space Index After Amyloid‐Targeting Disease‐Modifying Therapy in Alzheimer's Disease: A Preliminary Study","abstract":"Alzheimer's disease (AD) is characterized by the progressive accumulation of amyloid-β peptides in the brain parenchyma, and impairment of interstitial waste clearance via the glymphatic system is suggested as one contributing factor [1, 2]. Recently approved disease-modifying (DM) monoclonal antibodies, such as lecanemab, are expected to slow cognitive decline by improving amyloid β clearance [3-5]. Diffusion tensor imaging along the perivascular space (DTIALPS) index has emerged as a noninvasive surrogate marker suggested to be associated with glymphatic activity [6]. This index declines with normal aging and is significantly lower in patients with AD than in cognitively normal individuals [6-8]. Although DM therapy (DMT) may affect the DTI-ALPS index, no studies have examined longitudinal changes in the DTI-ALPS index following DMT initiation. Therefore, this study quantified the DTI-ALPS index in patients with AD before and 3 months after the initiation of amyloid-targeting DMT to generate provisional reference values for the longitudinal assessment of future DM-treated cohorts. This investigation comprised a two-step observational analysis. (1) From a publicly available Open Access Series of Imaging Studies (OASIS) dataset (http://oasis-brains.org/), cognitively normal volunteers (23 paired data) who underwent two identical DTI acquisitions were used solely to characterize within-participant variability and to derive the sample size requirement and associated 90% confidence interval (CI) limits for the subsequent equivalence test [9]. (2) Paired DTI-ALPS indices at baseline and 3 months after the initiation of DMT were evaluated at our institution. Participants were prospectively and consecutively recruited between December 1, 2023, and February 28, 2025. Included participants were: (i) diagnosed with AD by neurologists; (ii) underwent brain magnetic resonance imaging (MRI) as part of screening for DMT and subsequently initiated lecanemab therapy. Only participants who provided written informed consent were included. All DTI data were obtained from a 3T MRI system, Magnetom Vida (Siemens Healthineers, Erlangen, Germany; 20 channel head coil), with an identical singleshot echoplanar DTI protocol (b = 1000 s/mm2, 30 directions with one b0 volume). Baseline MRI was performed within 3 months before the first lecanemab dose, and follow-up MRI was performed exactly 3 months after treatment initiation. Before analysis, every DTI data was cleaned to reduce random noise, stripped of Gibbs ringing artifacts, corrected for motion and eddy current-related distortions, and adjusted for intensity bias using MRtrix3 (version 3.0.4; https://www.mrtrix.org). Subsequently, the functions VECREG, FLIRT, and FNIRT, provided by the FMRIB software library (FSL, version 6.0.7.3; https://www.fmrib.ox.ac.uk/fsl), were used for DTI vector reorientation, linear, and non-linear registration, respectively, using an automated calculation method of DTI-ALPS index [8]. Mean diffusivities along Dxx, Dyy, and Dzz within ROIs of projection and association fibers from bilateral hemispheres were averaged, yielding a single DTI-ALPS index. The detailed processing overview and script are presented in Figure 1 and Data S1, respectively. Repeated DTI-ALPS indices calculation of 23 OASIS volunteers yielded a within-participant standard deviation (SD) of 0.07. The data were used to characterize variability for sample-size planning and equivalence margins, not for cross-protocol comparisons. Setting an equivalence margin of δ = ±0.05 (≈0.7 SD) as clinically negligible for therapy-related changes, a two one-sided test (TOST; one-sided α = 0.05, power = 0.80) indicated that 13 paired participants would be sufficient. The 90% CI is the interval that corresponds to these dual α = 0.05 tests and is therefore standard in equivalence studies. The detailed volunteer data are shown as Supplement data. Then, baseline and three-month participants' DTI-ALPS indices were analyze","journal":"Journal of Magnetic Resonance Imaging","year":2025,"id":554095,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"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":404819,"name":"Hiroyuki Tatekawa","orcid":"0000-0002-8050-4895","position":1,"is_corresponding":false},{"id":1450978,"name":"Akitoshi Takeda","orcid":"0000-0003-4911-9320","position":2,"is_corresponding":false},{"id":1451412,"name":"Ayako Omori","orcid":null,"position":3,"is_corresponding":false},{"id":858636,"name":"Natsuko Atsukawa","orcid":"0009-0001-7170-1029","position":4,"is_corresponding":false},{"id":858633,"name":"Shu Matsushita","orcid":"0000-0003-1132-9736","position":5,"is_corresponding":false},{"id":858635,"name":"Daisuke Horiuchi","orcid":"0000-0002-8929-8098","position":6,"is_corresponding":false},{"id":858634,"name":"Hirotaka Takita","orcid":"0000-0003-2860-4503","position":7,"is_corresponding":false},{"id":858637,"name":"Taro Shimono","orcid":"0000-0001-5847-6587","position":8,"is_corresponding":false},{"id":59462,"name":"Daiju Ueda","orcid":"0000-0002-3878-3616","position":9,"is_corresponding":false},{"id":840253,"name":"Yoshiaki Itoh","orcid":"0000-0001-5731-798X","position":10,"is_corresponding":false},{"id":208000,"name":"Yukio Miki","orcid":"0000-0003-0621-0044","position":11,"is_corresponding":false},{"id":1450977,"name":"Tatsushi Oura","orcid":"0000-0002-0930-1032","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40922590","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":[]}