{"doi":"10.3389/fnins.2020.571480","title":"Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort","abstract":"Background: Dynamic contrast-enhanced (DCE) MRI using intravenous injection of gadolinium-based contrast agents (GBCAs) is commonly used for imaging blood-brain barrier (BBB) permeability. Water is an alternative endogenous tracer with limited exchange rate across the BBB. A direct comparison between BBB water exchange rate and BBB permeability to GBCA is missing. The purpose of this study was to directly compare BBB permeability to GBCA (Ktrans and k Gad = Ktrans/Vp) and water exchange rate (kw) in a cohort of elderly subjects at risk of cerebral small vessel disease (cSVD). Methods: Ktrans/k Gad and kw were measured by DCE-MRI and diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL), respectively, at 3 Tesla in 16 elderly subjects (3 male, age = 67.9 ± 3.0 yrs) at risk of cSVD. The test-retest reproducibility of kw measurements was evaluated with repeated scans ~6 weeks apart. Mixed effects linear regression was performed in the whole brain, gray matter (GM), white matter (WM), and 6 subcortical brain regions to investigate associations between Ktrans/k Gad and test-retest kw. In addition, kw and Ktrans/k Gad were compared in normal appearing white matter (NAWM), white matter hyperintensity (WMH) lesions and penumbra. Results: Significant correlation was found between kw and Ktrans only in WM (β = 6.7 × 10 4 , P = 0.036), caudate (β = 8.6 × 10 4 , P = 0.029), and middle cerebral artery (MCA) perforator territory (β = 6.9 × 10 4 , P = 0.009), but not in the whole brain, GM or rest 5 brain regions. Significant correlation was found between kw and k Gad in MCA perforator territory (β = 1.5 × 10 3 , P = 0.049), medial-temporal lobe (β = 3.5 × 10 3 , P = 0.032), and hippocampus (β = 3.4 × 10 3 , P = 0.038), but not in the rest brain regions. Good reproducibility of kw measurements (ICC=0.75) was achieved. Ktrans was significantly lower inside WMH than WMH penumbra (16.2%, P = 0.026), and k Gad was significantly lower in NAWM than in the WMH penumbra (20.8%, P < 0.001). Conclusion: kw provides a measure of water exchange rate across the BBB with good test-retest reproducibility. The BBB mechanism underlying kw and Ktrans/k Gad is likely to be different, as manifested by correlations in only three brain regions for each pair of comparison between kw and Ktrans or k Gad .","journal":"Frontiers in Neuroscience","year":2020,"id":55998,"datarank":0.6749714505495399,"base_score":4.499809670330265,"endowment":4.499809670330265,"self_citation_contribution":0.6749714505495399,"citation_network_contribution":0.0,"self_endowment_contribution":0.6749714505495399,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":288640,"name":"Kay Jann","orcid":"0000-0003-3574-0538","position":1,"is_corresponding":false},{"id":244997,"name":"J. Samantha","orcid":"0000-0003-3127-455X","position":2,"is_corresponding":false},{"id":290779,"name":"Lirong Yan","orcid":"0000-0002-5173-7059","position":3,"is_corresponding":false},{"id":290780,"name":"Axel Montagne","orcid":"0000-0001-5564-985X","position":4,"is_corresponding":false},{"id":281099,"name":"John M. Ringman","orcid":"0000-0001-5429-0777","position":5,"is_corresponding":false},{"id":288638,"name":"Berislav V. Zloković","orcid":"0000-0002-6802-8232","position":6,"is_corresponding":false},{"id":244996,"name":"Danny J.J. Wang","orcid":"0000-0002-0840-7062","position":7,"is_corresponding":false},{"id":290778,"name":"Xingfeng Shao","orcid":"0000-0002-4130-6204","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:05:49.581291Z","pmid":"33328848","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":[]}