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Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor imaging (DTI). We aimed to assess flortaucipir uptake across speech\u2010language\u2010related WM tracts identified using DTI tractography in PAOS. Twenty\u2010two patients with PAOS and 26 matched healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent MRI and flortaucipir\u2010PET. The patient population included patients with primary progressive apraxia of speech (PPAOS) and non\u2010fluent variant\/agrammatic primary progressive aphasia (agPPA). Flortaucipir PET scans and DTI were coregistered using rigid registration with a mutual information cost function in subject space. Alignments between DTI and flortaucipir PET were inspected in all cases. Whole\u2010brain tractography was calculated using deterministic algorithms by a tractography reconstruction tool (DSI\u2010studio) and specific tracts were identified using an automatic fiber tracking atlas\u2010based method. Fractional anisotropy (FA) and flortaucipir standardized uptake value ratios (SUVRs) were averaged across the frontal aslant tract, arcuate fasciculi, inferior frontal\u2010occipital fasciculus, inferior and middle longitudinal fasciculi, as well as the SMA commissural fibers. Reduced FA (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) and elevated flortaucipir SUVR (<jats:italic>p<\/jats:italic>\u2009=\u2009.0012) were observed in PAOS cases compared to controls across all combined WM tracts. For flortaucipir SUVR, the greatest differentiation of PAOS from controls was achieved with the SMA commissural fibers (area under the receiver operator characteristic curve [AUROC]\u2009=\u20090.83), followed by the left arcuate fasciculus (AUROC\u2009=\u20090.75) and left frontal aslant tract (AUROC\u2009=\u20090.71). Our findings demonstrate that flortaucipir uptake is increased across WM tracts related to speech\/language difficulties in PAOS.<\/jats:p>","DOI":"10.1002\/hbm.26704","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T06:44:59Z","timestamp":1717397099000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multimodal cross\u2010examination of progressive apraxia of speech by diffusion tensor imaging\u2010based tractography and <scp>Tau\u2010PET<\/scp> scans"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-6662","authenticated-orcid":false,"given":"Rodolfo G.","family":"Gatto","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nha Trang Thu","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Radiology 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