{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:39:48Z","timestamp":1790347188480,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Endowed Manitoba Public Insurance (MPI) Chair in Neuroscience\/TBI Research Endowment","doi-asserted-by":"publisher","award":["ALLRP-578524-22"],"award-info":[{"award-number":["ALLRP-578524-22"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Background: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This study aims to characterize the burden of impaired RAP in relation to other key components of cerebral physiology. Methods: Archived data from 379 moderate-to-severe TBI patients were analyzed using descriptive and threshold-based methods across three RAP states (impaired, intact\/transitional, and exhausted). Agglomerative hierarchical clustering, principal component analysis, and kernel-based clustering were applied to explore multivariate covariance structures. Then, high-frequency temporal analyses, including vector autoregressive integrated moving average impulse response functions (VARIMA IRF), cross-correlation, and Granger causality, were performed to assess dynamic coupling between RAP and other physiological signals. Results: Impaired and exhausted RAP states were associated with elevated intracranial pressure (p = 0.021). Regarding AMP, impaired RAP was associated with elevated levels, while exhausted RAP was associated with reduced pulse amplitude (p = 3.94 \u00d7 10\u22129). These two RAP states were also associated with compromised autoregulation and diminished perfusion. Clustering analyses consistently grouped RAP with its constituent signals (ICP and AMP), followed by brain oxygenation parameters (brain tissue oxygenation (PbtO2) and regional cerebral oxygen saturation (rSO2)). Cerebral autoregulation (CA) indices clustered more closely with RAP under impaired autoregulatory states. Temporal analyses revealed that RAP exhibited comparatively stronger responses to ICP and arterial blood pressure (ABP) at 1-min resolution. Moreover, when comparing ICP-derived and near-infrared spectroscopy (NIRS)-derived CA indices, they clustered more closely to RAP, and RAP demonstrated greater sensitivity to changes in these ICP-derived CA indices in high-frequency temporal analyses. These trends remained consistent at lower temporal resolutions as well. Conclusion: RAP relationships with other parameters remain consistent and differ meaningfully across compliance states. Integrating RAP into patient trajectory modelling and developing predictive frameworks based on these findings across different RAP states can map the evolution of cerebral physiology over time. This approach may improve prognostication and guide individualized interventions in TBI management. Therefore, these findings support RAP\u2019s potential as a valuable metric for bedside monitoring and its prospective role in guiding patient trajectory modeling and interventional studies in TBI.<\/jats:p>","DOI":"10.3390\/bioengineering12091006","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"1006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Relationship Between RAP and Multi-Modal Cerebral Physiological Dynamics in Moderate\/Severe Acute Traumatic Neural Injury: A CAHR-TBI Multivariate Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6669-3374","authenticated-orcid":false,"given":"Abrar","family":"Islam","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Price Faculty of Engineering, University of Manitoba, Winnipeg, MB R3T 5V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-008X","authenticated-orcid":false,"given":"Kevin Y.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Price Faculty of Engineering, University of Manitoba, Winnipeg, MB R3T 5V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-8624","authenticated-orcid":false,"given":"Donald","family":"Griesdale","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"Division of Critical Care, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4487-301X","authenticated-orcid":false,"given":"Mypinder","family":"Sekhon","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9121-2882","authenticated-orcid":false,"given":"Francis","family":"Bernard","sequence":"additional","affiliation":[{"name":"Section of Critical Care, Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Section of Neurosurgery, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2338-4364","authenticated-orcid":false,"given":"Eric P.","family":"Thelin","sequence":"additional","affiliation":[{"name":"Medical Unit Neurology, Karolinska University Hospital, 171 76 Stockholm, Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-2466","authenticated-orcid":false,"given":"Francois","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Section of Neurosurgery, Department of Surgery, University of Toronto, TO M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Critical Care Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Aries","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Maastricht University Medical Center+, School of Mental Health and Neurosciences, University Maastricht, 6211 LH Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-0189","authenticated-orcid":false,"given":"Logan","family":"Froese","sequence":"additional","affiliation":[{"name":"Medical Unit Neurology, Karolinska University Hospital, 171 76 Stockholm, Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-0510","authenticated-orcid":false,"given":"Frederick A.","family":"Zeiler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Price Faculty of Engineering, University of Manitoba, Winnipeg, MB R3T 5V6, Canada"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 5V6, Canada"},{"name":"Pan Am Clinic Foundation, Winnipeg, MB R3M 3E4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","article-title":"Traumatic Brain Injury: Integrated Approaches to Improve Prevention, Clinical Care, and Research","volume":"16","author":"Maas","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1227\/NEU.0000000000001432","article-title":"Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition","volume":"80","author":"Carney","year":"2017","journal-title":"Neurosurgery"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1007\/s00134-019-05805-9","article-title":"A Management Algorithm for Patients with Intracranial Pressure Monitoring: The Seattle 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