{"doi":"10.1101/2025.08.01.668145","title":"TRACC-PHYSIO: Time-domain Resolution-Aligned Cross-Correlation to estimate PHYSIOlogical coupling and time delays in dynamic MRI","abstract":"Abstract Physiological brain pulsations, primarily driven by cardiac and respiratory activity, play a key role in driving neurofluid circulation and waste clearance. Capturing the temporal dynamics of cardiac- and respiratory-driven brain pulsations (0.2-1.5 Hz) requires fast imaging with TRs near 100 ms, which is often unachievable in functional MRI or dynamic diffusion MRI. As a result, valuable physiological information remains hidden in these datasets. Here, we introduce TRACC-PHYSIO, a time-domain analytical framework designed to quantify physiological coupling and pulse time delays in dynamic MRI without requiring a fast acquisition. TRACC-PHYSIO uses cross-correlation to detect co-fluctuations between slowly sampled dynamic MRI data and simultaneously recorded physiological waveforms. It measures two key metrics: the peak Coupling Coefficient (peak CorrCoeff), quantifying the strength of co-fluctuations, and the TimeDelay, reflecting the relative arrival time of the physiological impulse in the brain with millisecond-level temporal resolution. The primary aim of this study is to validate TRACC-PHYSIO through systematic simulations that model realistic dynamic MR signals with mixed physiological components. We comprehensively evaluate TRACC-PHYSIO’s performance under a wide range of conditions, including varying cardiac-to-respiratory composition ratios, TRs, and acquisition times. Results demonstrate that TRACC-PHYSIO can robustly assess coupling strengths and time delays for both cardiac (TRACC-Cardiac) and respiratory (TRACC-Respiratory) components, even in datasets with long TRs up to 3 seconds. By enabling a reliable time-domain coupling analysis, TRACC-PHYSIO opens new avenues for revealing brain pulsation mechanisms and elucidating the physiological drivers of neurofluid dynamics in health and disease. This stimulation study provides a valuable reference for interpreting TRACC-PHYSIO results and understanding associated uncertainties in future applications. Highlights - TRACC-PHYSIO is a time-domain method developed to estimate cardiac and respiratory coupling and their pulsation time delays in dynamic MRI without requiring high temporal resolution. - TRACC-PHYSIO was validated through systematic simulations across varying physiological compositions and MR acquisition parameters. - Results demonstrated that TRACC-PHYSIO reliably quantifies cardiac and respiratory components in dynamic MR signals. - The stimulation study provides a useful reference for interpreting TRACC-PHYSIO results and understanding associated uncertainties in future applications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558672,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9491,"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":1459492,"name":"Jianing Zhang","orcid":"0000-0003-2964-0733","position":1,"is_corresponding":false},{"id":429987,"name":"Yunjie Tong","orcid":"0000-0001-6052-8913","position":2,"is_corresponding":false},{"id":297388,"name":"Qiuting Wen","orcid":"0000-0002-7885-4036","position":3,"is_corresponding":false},{"id":500687,"name":"Adam M. Wright","orcid":"0000-0001-9524-2210","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40766675","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":[]}