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A total of 1306 <jats:sup>123<\/jats:sup>I-FP-CIT-SPECT were included retrospectively. Binary classification as \u2018reduced\u2019 or \u2018normal\u2019 striatal <jats:sup>123<\/jats:sup>I-FP-CIT uptake by an experienced reader served as standard-of-truth. A custom-made 3-dimensional convolutional neural network (CNN) was trained for classification of the SPECT images with 1006 randomly selected images in three different settings: \u201cfull image\u201d, \u201cstriatum only\u201d (3-dimensional region covering the striata cropped from the full image), \u201cwithout striatum\u201d (full image with striatal region removed). The remaining 300 SPECT images were used to test the CNN classification performance. Layer-wise relevance propagation (LRP) was used for voxelwise quantification of the relevance for the CNN-based classification in this test set. Overall accuracy of CNN-based classification was 97.0%, 95.7%, and 69.3% in the \u201cfull image\u201d, \u201cstriatum only\u201d, and \u201cwithout striatum\u201d setting. Prominent contributions in the LRP-based relevance maps beyond the striatal signal were detected in insula, amygdala, ventromedial prefrontal cortex, thalamus, anterior temporal cortex, superior frontal lobe, and pons, suggesting that <jats:sup>123<\/jats:sup>I-FP-CIT uptake in these brain regions provides clinically useful information for the differentiation of neurodegenerative and non-neurodegenerative parkinsonian syndromes.<\/jats:p>","DOI":"10.1038\/s41598-021-02385-x","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T11:08:02Z","timestamp":1637838482000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Data-driven identification of diagnostically useful extrastriatal signal in dopamine transporter SPECT using explainable AI"],"prefix":"10.1038","volume":"11","author":[{"given":"Mahmood","family":"Nazari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kluge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivayla","family":"Apostolova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Klutmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharok","family":"Kimiaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-0724","authenticated-orcid":false,"given":"Ralph","family":"Buchert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"2385_CR1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0022-510x(73)90175-5","volume":"20","author":"H Bernheimer","year":"1973","unstructured":"Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. & Seitelberger, F. 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