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The new method is applied to characterise connectivity changes in the Alzheimer's disease (AD) continuum. The proposed twPC<\/jats:styled-content> samples PET<\/jats:styled-content> tracer uptake guided by the underlying white matter fibre\u2010tracking streamline point\u2010to\u2010point connectivity calculated from diffusion MRI (<\/jats:styled-content>dMRI)<\/jats:styled-content>. Using tau\u2010PET<\/jats:styled-content>, dMRI and T1<\/jats:styled-content>\u2010weighted MRI<\/jats:styled-content> from the Alzheimer's Disease Neuroimaging Initiative database, structural connectivity (SC<\/jats:styled-content>) and twPC<\/jats:styled-content> matrices were computed and analysed using the network\u2010based statistic (NBS) technique to examine topological alterations in early mild cognitive impairment (MCI<\/jats:styled-content>), late MCI<\/jats:styled-content> and AD<\/jats:styled-content> participants. Correlation analysis was also performed to explore the coupling between SC<\/jats:styled-content> and twPC<\/jats:styled-content>. The NBS analysis revealed progressive topological alterations in both SC<\/jats:styled-content> and twPC<\/jats:styled-content> as cognitive decline progressed along the continuum. Compared to healthy controls, networks with decreased SC<\/jats:styled-content> were identified in late MCI<\/jats:styled-content> and AD<\/jats:styled-content>, and networks with increased twPC<\/jats:styled-content> were identified in early MCI<\/jats:styled-content>, late MCI<\/jats:styled-content> and AD<\/jats:styled-content>. The altered network topologies were mostly different between twPC<\/jats:styled-content> and SC<\/jats:styled-content>, although with several common edges largely involving the bilateral hippocampus, fusiform gyrus and entorhinal cortex. Negative correlations were observed between twPC<\/jats:styled-content> and SC<\/jats:styled-content> across all subject groups, although displaying an overall reduction in the strength of anti\u2010correlation with disease progression. twPC<\/jats:styled-content> provides a new means for analysing subject\u2010specific PET<\/jats:styled-content> and MRI<\/jats:styled-content>\u2010derived information within a hybrid connectome using established network analysis methods, providing valuable insights into the relationship between structural connections and molecular distributions.<\/jats:p><\/jats:sec>Practitioner Points<\/jats:title>\nNew method is proposed to compute patient\u2010specific PET connectome guided by MRI fibre\u2010tracking.<\/jats:p><\/jats:list-item>\nTrack\u2010weighted PET connectivity (twPC) matrix allows to leverage PET and structural connectivity information.<\/jats:p><\/jats:list-item>\ntwPC was applied to dementia, to characterise the PET nework abnormalities in Alzheimer's disease and mild cognitive impairment.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/hbm.26659","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T06:55:08Z","timestamp":1710572108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel method for PET connectomics guided by fibre\u2010tracking MRI: Application to Alzheimer's disease"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-0711","authenticated-orcid":false,"given":"Zhuopin","family":"Sun","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Naismith","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre The University of Sydney Sydney New South Wales Australia"},{"name":"Faculty of Science, School of Psychology The University of Sydney Sydney New South Wales Australia"},{"name":"Charles Perkins Center The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Meikle","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre The University of Sydney Sydney New South Wales Australia"},{"name":"Sydney Imaging The University of Sydney Sydney New South Wales Australia"},{"name":"School of Health Sciences The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Calamante","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering The University of Sydney Sydney New South Wales Australia"},{"name":"Brain and Mind Centre The University of Sydney Sydney New South Wales Australia"},{"name":"Sydney Imaging The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00064"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263202"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10334-017-0608-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics9030115"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.12.054"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.08.099"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24711"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROIMAGE.2006.01.021"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"e_1_2_11_13_1","unstructured":"Dhollander T. &Connelly A.(2016).A novel iterative approach to reap the benefits of multi\u2010tissue CSD from just single\u2010shell (+ b\u2009=\u20090) diffusion MRI data A novel iterative approach to reap the benefits of multi\u2010tissue CSD. 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