Letter to the Editor Cardiac quadruple-fusion imaging: A brief report on a novel integrated multimodality approach for in vivo visualization of transplanted stem cells ☆ Michael Fiechter a, 1 , Jelena R. Ghadri a, b, 1 , Michèle Sidler c, d , Ulrich Martin e , Ulf Landmesser b , Philipp A. Kaufmann a, b , Thomas F. Lüscher b , Christian Templin b, e, ⁎ a Cardiovascular Center, Cardiac Imaging, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland b Cardiovascular Center, Cardiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland c Veterinary Anaesthesia Services—International, Winterthur, Switzerland d Musculoskeletal Research Unit (MRSU), Vetsuisse Faculty, University of Zurich, Switzerland e Leibniz Research Laboratories for Biotechnology and Artificial Organs, Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany article info Article history: Received 28 May 2012 Accepted 9 June 2012 Available online xxxx Keywords: Cardiac imaging SPECT CCTA NOGA hiPSCs A prerequisite for successful monitoring of stem cell therapy after myocardial infarction is the in vivo visualisation of transplanted cells [1]. Therefore, imaging techniques with a high sensitivity and spatial resolution are desirable. Current imaging modalities that have been advocated and used for in vivo tracking of stem cells include magnetic resonance imaging, nuclear imaging and bioluminescence imaging. However, each of these imaging modalities has its unique advantages and limitations with respect to cell detection sensitivity, specificity, temporal and spatial resolution [2–4]. While single photon emission computed tomography (SPECT) per- mits exact localization of increased radiotracer uptake in any plane, one major disadvantage is the lack of precise anatomic landmarks. Coronary computed tomography angiography (CCTA), on the other hand, allows accurate localization of anatomic structures, while lacking the ability to detect transplanted cells. NOGA-technology which was introduced primarily for the use in electrophysiology can differentiate viable from non-viable myocardium, and thus permits exact visualiza- tion of the injection points of transplanted stem cells in the border zone of viable and non-viable myocardial tissue to warrant a successful application in the target territory. An integrated modality approach is desirable to monitor stem cells after their implantation into infarcted myocardial tissue using simultaneously all 3 techniques. Recently, the feasibility of detecting 123 I labeled human induced pluripotent stem cells (hiPSCs) transfected with sodium–iodine symporter (NIS) in bor- der zones of infarcted territories by using cardiac hybrid imaging has been demonstrated by our group [5]. The aim of the current study was to establish a novel approach integrating all four imaging modalities, which would enable the detection of NIS-transfected hiPSCs in a porcine model of myocardial infarction revealing the exact anatomic location of the injected stem cells with the corresponding perfusion defect together with the related coronary vessels. Myocardial infarction in pigs was induced by 180-min percutaneous occlusion of the mid-segment left anterior descending artery followed by three-dimensional (3D) NOGA-mapping and intramyocardial injec- tion of 123 I labeled NIS-transfected hiPSCs into the border zones of the infarcted territory. Thereafter, 99m Tc-tetrofosmin SPECT was performed to verify the perfusion defect of the infarcted area and 123 I SPECT to detect successful transplantation of NIS-transfected hiPSCs into the myocardium. Finally, each pig underwent contrast enhanced CCTA with prospective ECG-triggering to image coronary and cardiac anatomy. Acquired image data from 99m Tc-tetrofosmin and 123 I SPECT were aligned and integrated on PMOD (V3.2, PMOD Technologies Ltd., Zurich, Switzerland) and then transferred to a dedicated workstation (Advantage Workstation 4.6, GE Healthcare) to generate SPECT/CCTA hybrid images (CardIQ Fusion software package, GE Healthcare). This cardiac hybrid images offer a 3D view of cardiac anatomy and perfusion together with exact localization of NIS-transfected hiPSCs as shown in rendered hybrid SPECT/CCTA volumes of perfusion (Fig. 1A) and 123 I (Fig. 1B) resulting in a 3D cardiac triple fusion for simultaneous detec- tion of previously injected and radiolabeled NIS-transfected hiPSCs together with myocardial perfusion and cardiac anatomy (Fig. 1C). International Journal of Cardiology xxx (2012) xxx–xxx ☆ Financial support: The study was supported by research grants of the Julia Bangerter- Rhyner Foundation and the Swiss Life Foundation as well as by the Swiss National Science Foundation (SNSF) and by the ZHIP (Zurich Center for Integrative Human Physiology, Zurich, Switzerland. ⁎ Corresponding author at: Department of Cardiology, University Hospital Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland. Tel.: +41 44 255 9585; fax: +41 44 255 4401. E-mail address: christian.templin@usz.ch (C. Templin). 1 The first two authors contributed equally to this work. IJCA-14996; No of Pages 2 0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.06.039 Contents lists available at SciVerse ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: Fiechter M, et al, Cardiac quadruple-fusion imaging: A brief report on a novel integrated multimodality approach for in vivo visualization of transplanted stem cells, Int J Cardiol (2012), doi:10.1016/j.ijcard.2012.06.039