Purpose: To develop a three-dimensional (two dimensions + time) convolutional neural network trained with displacement encoding with stimulated echoes (DENSE) data for displacement and strain analysis of cine MRI., Materials and Methods: In this retrospective multicenter study, a deep learning model (StrainNet) was developed to predict intramyocardial displacement from contour motion. Patients with various heart diseases and healthy controls underwent cardiac MRI examinations with DENSE between August 2008 and January 2022. Network training inputs were a time series of myocardial contours from DENSE magnitude images, and ground truth data were DENSE displacement measurements. Model performance was evaluated using pixelwise end-point error (EPE). For testing, StrainNet was applied to contour motion from cine MRI. Global and segmental circumferential strain (E cc ) derived from commercial feature tracking (FT), StrainNet, and DENSE (reference) were compared using intraclass correlation coefficients (ICCs), Pearson correlations, Bland-Altman analyses, paired t tests, and linear mixed-effects models., Results: The study included 161 patients (110 men; mean age, 61 years ± 14 [SD]), 99 healthy adults (44 men; mean age, 35 years ± 15), and 45 healthy children and adolescents (21 males; mean age, 12 years ± 3). StrainNet showed good agreement with DENSE for intramyocardial displacement, with an average EPE of 0.75 mm ± 0.35. The ICCs between StrainNet and DENSE and FT and DENSE were 0.87 and 0.72, respectively, for global E cc and 0.75 and 0.48, respectively, for segmental E cc . Bland-Altman analysis showed that StrainNet had better agreement than FT with DENSE for global and segmental E cc ., Conclusion: StrainNet outperformed FT for global and segmental E cc analysis of cine MRI. Keywords: Image Postprocessing, MR Imaging, Cardiac, Heart, Pediatrics, Technical Aspects, Technology Assessment, Strain, Deep Learning, DENSE Supplemental material is available for this article. © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: Y.W. Supported by the American Heart Association (2020AHAPRE0000203801); U.S. provisional patent applications serial numbers 63/149,900 ("System and Method for Improved Cardiac MRI Feature Tracking by Learning from Displacement-Encoded Imaging") and 63/408,760 ("Method and System for Strain Analysis that Includes CMR-trained StrainNet to Echocardiography"). C.S. U.S. provisional patent applications serial numbers 63/149,900 ("System and Method for Improved Cardiac MRI Feature Tracking by Learning from Displacement-Encoded Imaging") and 63/408,760 ("Method and System for Strain Analysis that Includes CMR-trained StrainNet to Echocardiography"). S.G. No relevant relationships. D.C.A. No relevant relationships. P.C. No relevant relationships. M.V. No relevant relationships. K.M. Co-applicant (2022) for National Health Service (NHS) Greater Glasgow and Clyde Endowment Funding (GN21CA412) for "Scar Characterisation with Cardiac MR to Predict Ventricular Arrhythmias" (£25 000); principal applicant (2021) for NHS Greater Glasgow and Clyde Endowment Funding (GN20CA408) for "Centre-specific Stress Perfusion Reference Ranges for the 3-T MRI Scanner" (£14 910); co-applicant (2021) for NHS Greater Glasgow and Clyde Endowment Funding (GN20ID164) for "CISCO-19 Visit 3" (£96 370); co-applicant (2021) for Chief Scientist Office–Long Term Effects of COVID (COV/LTE/20/10) for "Prevention and Early Treatment of COVID-19 Long Term Effects: A Randomised Clinical Trial of Resistance Exercise" (£288 660); principal applicant (2020) for Tenovus Scotland (S20-08) for "Investigating the Long-term Cardiac Sequelae of Trastuzumab Therapy" (£19 600); principal applicant (2022) for SoftMech Feasibility Funds for "Using Advanced CMR Techniques and Computational Modeling in Female Volunteers to Detect Pump Function Changes in Cancer Patients" (£10 000); principal applicant (2020) for Wellcome ISSF COVID Response Fund for "A Vascular Biology Nested Study within CISCO-19" (£10 000); co-applicant (2020) for Chief Scientist Office, Rapid Research COVID-19 for "Cardiovascular Imaging in SARS-CoV-2 (CISCO-19)" (COV/GLA/20/05) (£48, 618; MRI and CTCA scan costs in-kind); co-applicant (2020) for EPSRC Impact Acceleration Account (IAA) Cardiac Endotypes in COVID-19 for "Quantification and Mechanisms of Cardiac Injury" (£48 304) C.B. Employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genenetech, GSK, HeartFlow, Menarini, Neovasc, Novartis, Siemens Healthcare, and Valo Health, with grants, contracts, consulting fees, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events paid to the institution, University of Glasgow; named on a pending patent for the use of zibotentan for microvascular angina, patent held by the University of Glasgow; participation on PROTECT-TAVR UK DSMB (unpaid); president of the British Society of Cardiovascular Magnetic Resonance (unpaid); past member of the Clinical Trials Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) (unpaid); in-kind support for clinical research studies involving Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis, GSK, HeartFlow, Novartis, and Siemens Healthcare, by contract with the University of Glasgow. C.M.H. Supported by the National Institutes of Health (NIH). L.J. No relevant relationships. B.K.F. Grant funding from the NIH (NIH DP5 OD-012132, NIH P20 GM-103527, NIH UL1 TR-000117) made to the institution where some of the cardiac MRI data was collected; full-time employment with Tempus Labs that began in late 2021 after the work was completed. J.J.C. No relevant relationships. J.C. No relevant relationships. A.D.S. The CMR Unit, Royal Brompton Hospital, receives research support from Siemens. P.F.F. Contribution to this work was funded by the British Heart Foundation (BHF), grant number RG/19/1/34160. J.N.O. No relevant relationships. D.B.E. NIH grant numbers NIH National Heart, Lung, and Blood Institute (NHLBI) R01 131975 and 131823; joint 6/8ths Stanford University/Veterans Affairs (SU/VA) appointment specified by a formal Memorandum of Understanding between SU and the VA, there is no possibility of dual compensation for the same work, no conflict of interest regarding such work, and the overall set of responsibilities meets the test of reasonableness; support for the following listed projects and proposals includes support managed through SU and through the investigator’s VA appointment, Palo Alto Veterans Institute for Research (PAVIR) and the VA Palo Alto Health Care System, primary place of performance for all is SU: "High Resolution Whole-Breast MRI at 3.0T Major," research to develop much higher resolution breast MRI, allowing better classification of small lesions to prevent unnecessary biopsy and detect cancer earlier, active support, project number R01 EB009055, source of support is IH/NIBIB, primary place of performance is SU, March 2020–November 2023, total award amount (including indirect costs) is $2 559 180; "Using Atrial Mechanics to Identify Fibrosis in Patients with Atrial Fibrillation," to use MRI of atrial mechanics to identify localized fibrosis and hypothesize that attenuated mechanics provide a robust measure of atrial fibrosis, active support, project number, source of support is NIH/NHLBI, June 2020–May 2024, total award amount (including indirect costs) is $2 787 583; "Biomechanical Optimization of Cardiac Valve Repair Operations," to validate our findings using large animal cardiac surgery models, and then hopefully translate these discoveries directly to the operating room in the human clinical arena, active support, project number R01 HL152155, source of support is NIH/NHLBI, primary place of performance is SU, May 2020–April 2024, total award amount (including indirect costs) is $2 762 997; "Advanced MR Applications Development–Tiger Team Years 13 & 14," comprises five projects in neuroimaging, high-field, pediatric, body, and musculoskeletal MRI, to advance clinical imaging capabilities, with the goals to develop and evaluate MR pulse sequences and hardware, active support, project number A117, source of support is GE Healthcare, June 2020–October 2022, total award amount (including indirect costs) is $1 936 583; "GE Healthcare–Stanford Artificial Intelligence in Medical Imaging Research," to develop methods of upstream medical imaging artificial intelligence to optimize the selection, scheduling, protocoling, and execution of exams, active support, project number A113, A114, A118, A120, source of support is GE Healthcare, July 2020–June 2024, total award amount (including indirect costs) is $3 342 138; "Abbreviated Non-Contrast-Enhanced MRI for Breast Cancer Screening," to provide accurate, low-cost, comfortable, MRI screening without intravenous contrast media, in a 10-minute exam, which will ultimately enable more effective and comfortable breast cancer screening for millions of women for whom x-ray mammography is insufficient, active support, project number R01 CA249893, source of support is NIH/NCI, primary place of performance is SU, February 2021–January 2026, total award amount (including indirect costs) is $3 127 573; "Enabling the Next Generation of High Performance Pediatric Whole-Body MR Imaging," to create and validate the next generation systems for pediatric MRI, active support, project number U01 EB029427, source of support is NIH/NIBIB, August 2020–July 2025, total award amount (including indirect costs) is $4 189 084; "Improved Diagnostic MRI Around Metallic Implants," active support, project number SPO#192723, source of support is the University of Southern California/NIH, February 2022–November 2026, total award amount (including indirect costs) is $967 045; "MR/PET Motion Correction from Coil Fingerprints," active support, project number, R01 EB029306, source of support is the NIH, September 2022–January 2024, total award amount (including indirect costs) is $1 261 824; "Developing ultra high field connectome hardware for order-of-magnitude increase in MRI sensitivity," pending support, project number SPO#280964, source of support is the NIH, primary place of performance is SU, July 1, 2023–June 30, 2028, total award amount (including indirect costs) is $4 403 210; "Fast and Accurate Cardiovascular 4D-Flow MRI for Pediatrics," pending support, project number SPO#232860, source of support is the NIH, April 1, 2023–March 31, 2028, total award amount (including indirect costs) is $3 861 471; projects managed and/or administered by PAVIR and VAPAHCS: "Using Atrial Mechanics to Identify Fibrosis in Patients with Atrial Fibrillation," to use MRI of atrial mechanics to identify localized fibrosis and hypothesize that attenuated mechanics provide a robust measure of atrial fibrosis, active support, project number R01 HL152256, source of support is NIH/NHLBI, June 2020–May 2024, total award amount (including indirect costs) is $271,187; "Implementing the Enhanced Liver Fibrosis (ELF) test to optimize prognostic screening and monitoring of hepatic fibrosis among patients at risk for non-alcoholic fatty liver disease (NAFLD)," to improve clinical care by using ELF to identify high-risk patients with hepatic fibrosis compared to standard-of-care and monitor patients for rapid disease progression or response to treatment, active support, project number C00239205, source of support is Siemens Medical Solutions USA, primary place of performance is VAPAHCS, September 2021–October 2024, total award amount (including indirect costs) is $718 147; "Abbreviated US and MRI versus FibroScan for diffuse liver disease," to improve clinical care by comparing the accuracy of vibration-controlled transient elastography (VCTE), US, and MRI for assessment of NAFLD/NASH and to introduce new US and MRI techniques to improve detection of NAFLD/NASH, active support, source of support is Siemens Medical Solutions USA, primary place of performance is VAPAHCS, September 2021–October 2024, total award amount (including indirect costs) is $551 656; author’s graduate students receive in-kind contributions. K.C.B. NHLBI grant, AHA grant, Medtronic grant, Siemens; consulting fees from Medtronic; payment or honoraria for speaker, ACC; US patent planned, issued, or pending; participation on a Data Safety Monitoring Board or Advisory Board for Left v. Left RCT funded by PCORI, 2022-present; vice-chair, HRS, research committee chair, SCMR, Clinical Trials Committee (starting in early February 2023, previously a member of the committee for several years), grant reviewer, NIH; research funding gift from Seraph Foundation. F.H.E. Research support from Siemens Healthineers Ivy Biomedical Innovation Fund; patents planned, issued, or pending, PCT/US2022/014903 Intramyocardial Tissue Displacement and Motion Measurement and Strain Analysis from MRI Cine Images Using DENSE Deep Learning; patent application number 63/408,760 entitled "Method and System for Strain Analysis that Includes CMR-trained StrainNet to Echocardiography.”, (© 2023 by the Radiological Society of North America, Inc.)