Molecular multimodality imaging: has a long-standing dream come true?

This editorial refers to ‘Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo’, by T. Hara et al., on page 447. Intravascular imaging has incrementally gained in clinical relevance in recent years. First triggered by the introduction of intravascular ultrasound >25 years ago,1 interest has recently been augmented by the widespread implementation of optical coherence tomography (OCT) in cardiac catheterization laboratories. OCT, because of its outstanding spatial resolution in the range of 10–20 μm relative to comparative invasive and non-invasive imaging modalities, has been charged with great expectations regarding its potential to advance our capabilities in detecting and characterizing vascular pathologies. In particular for patients undergoing stent implantation, OCT has been put forward as a promising tool to assess the status of vascular healing, which has been identified as an important landmark in pathology studies determining the risk of acute and late thrombotic events in stented coronary arteries.2 Furthermore, the ongoing dispute about the optimal duration of dual antiplatelet therapy following drug-eluting stent (DES) implantation,3,4 along with demands to personalize clinical decision-making in this regard, further fuelled the need for clinical surrogate parameters enabling clinicians to appreciate the status of vascular healing. However, despite the unequivocal agreement among interventional cardiologists that OCT is the most likely technology to fulfil these expectations, evidence derived from prospective clinical trials is still lacking to date. Furthermore, the unconditional acceptance of OCT to detect vascular pathologies reliably has recently been challenged by reports describing its limitations in differentiating critical components of the status of vascular healing following stent implantation, such as endothelialization and fibrin deposition.5 In this vein, in the current issue of the journal, Hara et al.6 report a novel combination imaging application of near infrared fluorescence (NIRF) and optical frequency domain imaging (OFDI). The authors utilized a near infrared (NIR) visible dye tagged to a peptide recognizing fibrin deposition in combination with OFDI after stent implantation in rabbit aorta. The study provided sound evidence of the system's feasibility in advancing OCT-derived information on strut coverage by specific imaging of fibrin deposition, which was shown not only to be significantly different among bare metal stents and DES at a 7-day time point but also to exhibit relevant dynamic changes between 7 and 28 days in this model. In this regard, the classical binomial metric of strut coverage derived from OCT image analysis was expanded using NIRF–OFDI to depict the principal presence or absence of fibrin deposition, a marker of delayed arterial healing. Proof-of-principle for the specific detection of fibrin was achieved by elaborate co-registration of longitudinal NIRF–OFDI image views with en face epifluorescent capturing of emission signals in the NIR range. In addition to that, cross-sectional co-registration was also performed following comparison of light microscopic sections with tomographic views of the combined NIRF–OFDI system.