BackgroundCardiac diffusion tensor imaging (cDTI) is an emerging technique for microstructural characterization of the heart and has shown clinical potential in a range of cardiomyopathies. However, there is substantial variation reported for in vivo cDTI results across the literature, and sensitivity of cDTI to differences in imaging sites, scanners, acquisition protocols, and post-processing methods remains incompletely understood.MethodsSIGNET is a prospective multi-center, observational study in traveling and non-traveling healthy volunteers. The study was initiated by the executive board of the Society of Cardiovascular Magnetic Resonance (SCMR) Cardiac Diffusion Special Interest Group (SIG) as a follow-up to a previous multi-center study on phantom validation of cardiac DTI and a recently published SCMR consensus statement on cardiac diffusion MRI. The study has been developed by the Project Management Committee in consultation with the SCMR cardiac diffusion SIG, which includes international experts in cardiac diffusion MRI. To date, more than 20 international institutions have engaged with the study, including sites that are new to cardiac DTI, making this the largest collaborative effort in the field.DiscussionSIGNET will provide important information about the key sources of variation in cardiac DTI. This will help rationalize strategies for addressing and minimizing such variation. Harmonization of protocols in this and future studies will underpin efforts to translate cardiac DTI for clinical application.