The Impact of Temporal Variation in Indocyanine Green Administration on Tumor Identification During Fluorescence Guided Breast Surgery

Background On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. Methods In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected similar to 25 min prior to tumor excision, and in the second 'angiography' cohort, similar to 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. Results The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 +/- 1.74 vs 2.10 +/- 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). Discussion ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.