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This study introduces a deep learning-based image registration framework specifically for arterial spin labeling (ASL) imaging. ASL is a magnetic resonance imaging technique that modifies the longitudinal magnetization of blood perfusing the kidney using a series of radiofrequency pulses combined with slice-selective gradients. After tagging the arterial blood, label images are captured following a delay, allowing the tagged blood bolus to enter the renal tissue, while control images are acquired without tagging the arterial spins. Given that perfusion maps are generated at the pixel level by subtracting control images from label images and considering the relatively small signal intensity difference, precise alignment of these images is crucial to minimize motion artefacts and prevent significant errors in perfusion calculations. Moreover, due to the extended ASL acquisition times and the anatomical location of the kidneys, renal images are often susceptible to pulsation, peristalsis, and breathing motion. These motion-induced noises and other instabilities can adversely affect ASL imaging outcomes, making image registration essential. However, research on renal MRI registration, particularly with respect to learning-based techniques, remains limited, with even less focus on renal ASL. Our study proposes a learning-based image registration approach that builds upon VoxelMorph and introduces groupwise inference as a key enhancement. The dataset includes 2448 images of transplanted kidneys (TK) and 2456 images of healthy kidneys (HK). We compared the automatic image registration results with the widely recognized optimization method Elastix. The model\u2019s performance was evaluated using the mean structural similarity index (MSSIM), normalized correlation coefficient (NCC), temporal signal-to-noise ratio (TSNR) of the samples, and the mean cortical signal (CSIM) in perfusion-weighted images, thereby extending the evaluation beyond traditional similarity-based metrics. Our method achieved superior image registration performance, with peak NCC (0.987\u2009\u00b1\u20090.006) and MSSIM (0.869\u2009\u00b1\u20090.048) values in the kidney region, significantly surpassing Elastix and the unregistered series (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) on TK and HK datasets. Regularization analysis showed that higher \u03bb values (1, 2) produced smoother deformation fields, while moderate \u03bb values (0.5, 0.9) balanced smoothness and detail, maintaining low non-positive Jacobian percentages (&lt;1%) comparable to Elastix. Additionally, our method improved CSIM by 14.3% (2.304\u2009\u00b1\u20091.167) and TSNR by 13.1% (3.888\u2009\u00b1\u20092.170) in TK, and achieved up to 13.2% (CSIM) and 29.8% (TSNR) enhancements in HK, demonstrating robustness and improved signal quality across datasets and acquisition techniques.<\/jats:p>","DOI":"10.1007\/s00521-025-11000-3","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T18:00:47Z","timestamp":1738346447000},"page":"8347-8369","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Advancing ASL kidney image registration: a tailored pipeline with VoxelMorph"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-0929","authenticated-orcid":false,"given":"Anne","family":"Oyarzun-Dome\u00f1o","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izaskun","family":"Cia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca","family":"Echeverria-Chasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda A.","family":"Fern\u00e1ndez-Seara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma L.","family":"Martin-Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Garcia-Fernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gorka","family":"Bastarrika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Navallas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arantxa","family":"Villanueva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"issue":"1","key":"11000_CR1","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1109\/TMI.2009.2035616","volume":"29","author":"S Klein","year":"2010","unstructured":"Klein S, Staring M, Murphy K, Viergever MA, Pluim JPW (2010) Elastix: a toolbox for intensity-based medical image registration. 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