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However, current nuclear medicine modalities face challenges like low spatial resolution and long acquisition times which limit clinical utility to non-emergency settings and often placing extra financial burden on the patient. This study introduces a novel deep learning approach to predict perfusion imaging from non-contrast inhale and exhale computed tomography scans (IE-CT).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We developed a U-Net Transformer architecture modified for Siamese IE-CT inputs, integrating insights from physical models and utilizing a self-supervised learning strategy tailored for lung function prediction. We aggregated 523\u00a0IE-CT images from nine different 4DCT imaging datasets for self-supervised training, aiming to learn a low-dimensional IE-CT feature space by reconstructing image volumes from random data augmentations. Supervised training for perfusion prediction used this feature space and transfer learning on a cohort of 44 patients who had both IE-CT and single-photon emission CT (SPECT\/CT) perfusion scans.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Testing with random bootstrapping, we estimated the mean and standard deviation of the spatial Spearman correlation between our predictions and the ground truth (SPECT perfusion) to be 0.742\u2009\u00b1\u20090.037, with a mean median correlation of 0.792\u2009\u00b1\u20090.036. These results represent a new state-of-the-art accuracy for predicting perfusion imaging from non-contrast CT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our approach combines low-dimensional feature representations of both inhale and exhale images into a deep learning model, aligning with previous physical modeling methods for characterizing perfusion from IE-CT. This likely contributes to the high spatial correlation with ground truth. With further development, our method could provide faster and more accurate lung function imaging, potentially expanding its clinical applications beyond what is currently possible with nuclear medicine.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11548-025-03323-2","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T11:12:28Z","timestamp":1737371548000},"page":"959-970","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perfusion estimation from dynamic non-contrast computed tomography using self-supervised learning and a physics-inspired U-net transformer architecture"],"prefix":"10.1007","volume":"20","author":[{"given":"Yi-Kuan","family":"Liu","sequence":"first","affiliation":[]},{"given":"Jorge","family":"Cisneros","sequence":"additional","affiliation":[]},{"given":"Girish","family":"Nair","sequence":"additional","affiliation":[]},{"given":"Craig","family":"Stevens","sequence":"additional","affiliation":[]},{"given":"Richard","family":"Castillo","sequence":"additional","affiliation":[]},{"given":"Yevgeniy","family":"Vinogradskiy","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0523-487X","authenticated-orcid":false,"given":"Edward","family":"Castillo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"issue":"9","key":"3323_CR1","doi-asserted-by":"publisher","first-page":"5657","DOI":"10.1002\/mp.16369","volume":"50","author":"JR Astley","year":"2023","unstructured":"Astley JR, Biancardi AM, Marshall H, Hughes PJC, Collier GJ, Hatton MQ, Wild JM, Tahir BA (2023) A hybrid model- and deep learning-based framework for functional lung image synthesis from multi-inflation CT and hyperpolarized gas MRI. 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