Abstract:Coronary Computed Tomography Angiography (CCTA) provides information on the presence, extent, and severity of obstructive coronary artery disease. Large-scale clinical studies analyzing CCTA-derived metrics typically require ground-truth validation in the form of high-fidelity 3D intravascular imaging. However, manual rigid alignment of intravascular images to corresponding CCTA images is both time consuming and user-dependent. Moreover, intravascular modalities suffer from several non-rigid motion-induced distortions arising from distortions in the imaging catheter path. To address these issues, we here present a semi-automatic segmentation-based framework for both rigid and non-rigid matching of intravascular images to CCTA images. We formulate the problem in terms of finding the optimal \emph{virtual catheter path} that samples the CCTA data to recapitulate the coronary artery morphology found in the intravascular image. We validate our co-registration framework on a cohort of $n=40$ patients using bifurcation landmarks as ground truth for longitudinal and rotational registration. Our results indicate that our non-rigid registration significantly outperforms other co-registration approaches for luminal bifurcation alignment in both longitudinal (mean mismatch: 3.3 frames) and rotational directions (mean mismatch: 28.6 degrees). By providing a differentiable framework for automatic multi-modal intravascular data fusion, our developed co-registration modules significantly reduces the manual effort required to conduct large-scale multi-modal clinical studies while also providing a solid foundation for the development of machine learning-based co-registration approaches.