{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:34:28Z","timestamp":1788510868105,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Respiratory motion irregularities in lung cancer patients are common and can be severe during multi\u2010fractional (\u223c20 mins\/fraction) radiotherapy. However, the current clinical standard of motion management is to use a single\u2010breath respiratory\u2010correlated four\u2010dimension computed tomography (RC\u20104DCT or 4DCT) to estimate tumor motion to delineate the internal tumor volume (ITV), covering the trajectory of tumor motion, as a treatment target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To develop a novel multi\u2010breath time\u2010resolved (TR) 4DCT using the super\u2010resolution reconstruction framework with TR 4D magnetic resonance imaging (TR\u20104DMRI) as guidance for patient\u2010specific breathing irregularity assessment, overcoming the shortcomings of RC\u20104DCT, including binning artifacts and single\u2010breath limitations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six lung cancer patients participated in the IRB\u2010approved protocol study to receive multiple T1w MRI scans, besides an RC\u20104DCT scan on the simulation day, including 80 low\u2010resolution (lowR: 5\u00a0\u00d7\u00a05\u00a0\u00d7\u00a05\u00a0mm<jats:sup>3<\/jats:sup>) free\u2010breathing (FB) 3D cine MR<jats:sup>FB<\/jats:sup> images in 40\u00a0s (2\u00a0Hz) and a high\u2010resolution (highR: 2\u00a0\u00d7\u00a02\u00a0\u00d7\u00a02\u00a0mm<jats:sup>3<\/jats:sup>) 3D breath\u2010hold (BH) MR<jats:sup>BH<\/jats:sup> image for each patient. A CT (1\u00a0\u00d7\u00a01\u00a0\u00d7\u00a03\u00a0mm<jats:sup>3<\/jats:sup>) image was selected from 10\u2010bin RC\u20104DCT with minimal binning artifacts and a close diaphragm match (&lt;1\u00a0cm) to the MR<jats:sup>BH<\/jats:sup> image. A mutual\u2010information\u2010based Freeform deformable image registration (DIR) was used to register the CT and MR<jats:sup>BH<\/jats:sup> via the opposite directions (namely F1:  and F2: ) to establish CT\u2010MR voxel correspondences. An intensity\u2010based enhanced Demons DIR was then applied for , in which the original MR<jats:sup>BH<\/jats:sup> was used in D1: , while the deformed MR<jats:sup>BH<\/jats:sup> was used in D2:. The deformation vector fields (DVFs) obtained from each DIR were composed to apply to the deformed CT (D1) and original CT (D2) to reconstruct TR\u20104DCT images. A digital 4D\u2010XCAT phantom at the end of inhalation (EOI) and end of exhalation (EOE) with 2.5\u00a0cm diaphragmatic motion and three spherical targets (\u03d5\u00a0=\u00a02, 3, 4\u00a0cm) were first tested to reconstruct TR\u20104DCT. For each of the six patients, TR\u20104DCT images at the EOI, middle (MID), and EOE were reconstructed with both D1 and D2 approaches. TR\u20104DCT image quality was evaluated with mean distance\u2010to\u2010agreement (MDA) at the diaphragm compared with MR<jats:sup>FB<\/jats:sup>, tumor volume ratio (TVR) referenced to MR<jats:sup>BH<\/jats:sup>, and tumor shape difference (DICE index) compared with the selected input CT. Additionally, differences in the tumor center of mass (|\u2206COM<jats:sup>D1\u2013D2<\/jats:sup>|), together with TVR and DICE comparison, was assessed in the D1 and D2 reconstructed TR\u20104DCT images.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the phantom, TR\u20104DCT quality is assessed by MDA\u00a0=\u00a02.0\u00a0\u00b1\u00a00.8\u00a0mm at the diaphragm, TVR\u00a0=\u00a00.8\u00a0\u00b1\u00a00.0 for all tumors, and DICE\u00a0=\u00a00.83\u00a0\u00b1\u00a00.01, 0.85\u00a0\u00b1\u00a00.02, 0.88\u00a0\u00b1\u00a00.01 for \u03d5\u00a0=\u00a02, 3, 4\u00a0cm tumors, respectively. In six patients, the MDA in diaphragm match is \u20131.6\u00a0\u00b1\u00a03.1\u00a0mm (D1) and 1.0\u00a0\u00b1\u00a03.9\u00a0mm (D2) between the reconstructed TR\u20104DCT and lowR MR<jats:sup>FB<\/jats:sup> among 18 images (3 phases\/patient). The tumor similarity is TVR\u00a0=\u00a01.2\u00a0\u00b1\u00a00.2 and DICE\u00a0=\u00a00.70\u00a0\u00b1\u00a00.07 for D1 and TVR\u00a0=\u00a01.4\u00a0\u00b1\u00a00.3 (D2) and DICE\u00a0=\u00a00.73\u00a0\u00b1\u00a00.07 for D2. The tumor position difference is |\u2206COM<jats:sup>D1\u2013D2<\/jats:sup>|\u00a0=\u00a01.2\u00a0\u00b1\u00a00.8\u00a0mm between D1 and D2 reconstructions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The feasibility of super\u2010resolution reconstruction of multi\u2010breathing\u2010cycle TR\u20104DCT is demonstrated and image quality at the diaphragm and tumor is assessed in both the 4D\u2010XCAT phantom and six lung cancer patients. The similarity of D1 and D2 reconstruction suggests consistent and reliable DIR results. Clinically, TR\u20104DCT has the potential for breathing irregularity assessment and dosimetry evaluation in radiotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.17487","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T16:14:18Z","timestamp":1729959258000},"page":"504-517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Super\u2010resolution reconstruction of time\u2010resolved four\u2010dimensional computed tomography (TR\u20104DCT) with multiple breathing cycles based on TR\u20104DMRI"],"prefix":"10.1002","volume":"52","author":[{"given":"Yilin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Physics Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Kentucky  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