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Meas."],"published-print":{"date-parts":[[2026,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cerebrovascular reactivity (CVR) to CO\n                    <jats:sub>2<\/jats:sub>\n                    is increasingly used as an index of cerebrovascular health and function in trials in cerebral small vessel disease (CSVD). Further work is needed to determine the validity and optimal parameters of this technique. In 75 CSVD patients in the placebo-controlled, crossover OxHARP trial of sildenafil, agreement and reproducibility of baseline (1st visit) and placebo visit CVR was derived comparing 4% and 6% CO\n                    <jats:sub>2<\/jats:sub>\n                    exposure. Peak response to each dose was used to estimate CVR (\u0394 cerebral blood velocity\/ \u0394 end-tidal CO\n                    <jats:sub>2<\/jats:sub>\n                    ) using absolute (cm.s\n                    <jats:sup>\u20131<\/jats:sup>\n                    \/etCO\n                    <jats:sub>2<\/jats:sub>\n                    %), fully standardised (%\u0394\/%\u0394) or semi-standardised (%\u0394\/etCO\n                    <jats:sub>2<\/jats:sub>\n                    %) approaches, and compared to CVR from delay-shifted, beat-to-beat associations from general linear models (GLM). Single-point measurements showed less inter- and intra-participant variability. The 6% CO\n                    <jats:sub>2<\/jats:sub>\n                    prompted higher absolute and standardised CVR values, although this was not observed with the semi-standardised of analysis. CVR estimates using absolute values showed comparable inter- and intra-participant variability across CO\n                    <jats:sub>2<\/jats:sub>\n                    challenges. However, reproducibility improved when CVR values were standardised following exposure to 6% CO\n                    <jats:sub>2<\/jats:sub>\n                    or derived using GLM that incorporated data from both 4% and 6% CO\n                    <jats:sub>2<\/jats:sub>\n                    data. The strongest agreement between CVR methods was achieved with analyses using absolute values. CVR assessments were reproducible, but this reliability was influenced by CO\n                    <jats:sub>2<\/jats:sub>\n                    dose and the analytical approach. While single-point measurements showed the best inter- and intra-participant variability, overall, CVR estimation using a GLM demonstrated a superior test-retest reliability across visits.\n                  <\/jats:p>","DOI":"10.1088\/1361-6579\/aeac99","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:52:21Z","timestamp":1790376741000},"page":"105013","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reliability and agreement between alternative CO\n                    <sub>2<\/sub>\n                    paradigms for assessment of cerebrovascular reactivity in cerebral small vessel disease"],"prefix":"10.1088","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9104-3222","authenticated-orcid":true,"given":"Osian","family":"Llwyd","sequence":"first","affiliation":[{"name":"University of Oxford"},{"name":"John Radcliffe Hospital"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4049-2364","authenticated-orcid":true,"given":"Karolina","family":"Feakins","sequence":"additional","affiliation":[{"name":"University of Oxford"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Catriona","family":"Stewart","sequence":"additional","affiliation":[{"name":"University of Oxford"},{"name":"University of St Andrews"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"James","family":"Thomas","sequence":"additional","affiliation":[{"name":"University of Oxford"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Alastair","family":"Webb","sequence":"additional","affiliation":[{"name":"University of Oxford"},{"name":"Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"266","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"pmeaaeac99bib1","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1152\/ajpregu.91008.2008","type":"journal-article","article-title":"Integration of cerebrovascular CO 2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation","volume":"296","author":"Ainslie","year":"2009","journal-title":"Am. 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