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We developed a 3D deep convolutional neural network to learn distinguishable DAT features for the differential diagnosis of parkinsonism. A full-gradient saliency map approach was employed to investigate the functional basis related to the decision mechanism of the network. Furthermore, deep-learning-guided radiomics features and quantitative analysis were compared with their conventional counterparts to further interpret the performance of deep learning.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The proposed network achieved area under the curve of 0.953 (sensitivity 87.7%, specificity 93.2%), 0.948 (sensitivity 93.7%, specificity 97.5%), and 0.900 (sensitivity 81.5%, specificity 93.7%) in the cross-validation, together with sensitivity of 90.7%, 84.1%, 78.6% and specificity of 88.4%, 97.5% 93.3% in the blind test for the differential diagnosis of IPD, MSA and PSP, respectively. The saliency map demonstrated the most contributed areas determining the diagnosis located at parkinsonism-related regions, e.g., putamen, caudate and midbrain. The deep-learning-guided binding ratios showed significant differences among IPD, MSA and PSP groups (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), while the conventional putamen and caudate binding ratios had no significant difference between IPD and MSA (<jats:italic>P<\/jats:italic>\u2009=\u20090.24 and <jats:italic>P<\/jats:italic>\u2009=\u20090.30). Furthermore, compared to conventional radiomics features, there existed average above 78.1% more deep-learning-guided radiomics features that had significant differences among IPD, MSA and PSP.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study suggested the developed deep neural network can decode in-depth information from DAT and showed potential to assist the differential diagnosis of parkinsonism. The functional regions supporting the diagnosis decision were generally consistent with known parkinsonian pathology but provided more specific guidance for feature selection and quantitative analysis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-022-05804-x","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T09:06:55Z","timestamp":1652951215000},"page":"2798-2811","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Decoding the dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning"],"prefix":"10.1007","volume":"49","author":[{"given":"Yu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjie","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengtao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhao","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Bassetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schwaiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Rominger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuantao","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuangyu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"5804_CR1","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1093\/brain\/awf080","volume":"125","author":"AJ Hughes","year":"2002","unstructured":"Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. 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