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Hybrid imaging has proven to be a major innovation in nuclear medicine, allowing the fusion of functional information with anatomical detail. In the past, the use of hybrid imaging such as PET-CT, PET-MRI and SPECT-CT has been of great clinical benefit; however, these scanners are relatively large and bulky. We have developed and investigated the clinical application of a compact small field of view hybrid gamma camera (HGC) that is suitable for small-organ imaging at the patient bedside.The HGC – consisting of a CsI(Tl) scintillation crystal coupled to an electron-multiplying charge-coupled device and an optical camera – was used in this study. Eligible patients attending the nuclear medicine clinic at Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK, were invited to take part in this study. Following the standard injection of either a 99mTc-labelled or 123I-labelled radiopharmaceutical, images of the patient were acquired using the HGC and presented in a fused optical-gamma display.There were 24 patients enrolled in the study (age range between 30 and 83 years, mean: 58.6 years), images of 18 of whom were successfully acquired. These included patients who were undergoing bone, thyroid, lacrimal drainage, DaTscan and lymphatic imaging. In general, the small field of view system was well suited to small-organ imaging. The uptake could be clearly seen in relation to the patient surface anatomy and showed particular promise for lymphatic, thyroid and lacrimal drainage studies.This pilot study has demonstrated the first clinical results of hybrid optical-gamma imaging in patients. The use of this system has raised new possibilities for small-organ imaging, in which the localization of radiopharmaceutical uptake can be presented in an anatomical context using optical imaging. The compact nature of the hybrid system offers the potential for bedside investigations and intraoperative use.