Abstract Percutaneous sampling of focal hepatic lesions is a cornerstone in the management of patients with hepatic pathology. The advent of advanced imaging has improved the sensitivity for lesion detection; however small lesions often lack specific features to allow for reliable non-invasive characterization, resulting in an increase in the number of biopsies for such hepatic lesions over the past decade. Accuracy of a focal hepatic biopsy is essential, as a false negative biopsy can have a devastating impact on a patient's treatment. In a retrospective study, up to 45% of small hepatic lesions were insufficiently visualized with the biopsy needle in place and had a false negative rate, defined as the number of patients with benign biopsies who were subsequently found to have malignant lesions at the attempted site of biopsy, of 37% for hepatocellular carcinomas. Thus, there is a significant need for improved methods for accurately sampling hepatic lesions. Recently, it was discovered that indocyanine green (ICG), a clinically approved near infrared fluorochrome, accumulates in hepatic foci such as hepatocellular carcinomas and hepatic colorectal metastases, resulting in a high target to background ratio when visualized using near infrared light. The PI of this proposal has led the first human experience, at MGH, combining optical imaging using ICG with interventional radiology percutaneous hepatic sampling. Independently, the intramural PI of this proposal has pioneered the development and clinical trials of electromagnetic (EM) navigation techniques for interventional radiology guided percutaneous sampling at the NIH Clinical Center – Center for Interventional Oncology (CIO). We propose to build upon a longstanding collaboration between the extramural and intramural PIs, and combine these two intrinsically synergistic, recent advances in the field of interventional radiology. The EM guided devices navigate the biopsy needle close to imaged lesions and can be thought of as far-field optimized; the optical imaging devices provide real- time feedback to assess if needle cores are appropriately located within small hepatic tumors and can be thought of as near-field devices. This first-in-man assessment of the new, proposed intramural-extramural jointly developed device will take place at the NIH CC-CIO. This jointly created and iteratively optimized device will help to improve patient care through improved diagnostic accuracy.