Methylene Blue–Based Near-Infrared Fluorescence Imaging for Breast Cancer Visualization in Resected Human Tissues

Abstract

Breast-conserving surgery is facing the challenge of objective tumor margin identification intraoperatively. Near-infrared fluorescence imaging would be an ideal approach to visualize tumor margins during surgeries. In this preliminary study, the feasibility of methylene blue–based near-infrared fluorescence imaging technique for breast cancer detection was assessed in resected human breast specimens after breast cancer surgeries. Thirty patients with breast cancer scheduled for surgical treatment were enrolled, including 10 patients with preoperative chemotherapy and 20 patients without. Each of them received an injection of 1 mg/kg methylene blue intravenously 3 hours before the surgery. Then, a home-developed methylene blue–specific near-infrared fluorescence imaging system was employed to image the resected breast tissues and identify the tumor by the fluorescence contrast. Specimens were taken for pathological examinations as the reference. There were no severe adverse events attributable to methylene blue. Of 20 patients, who did not receive preoperative chemotherapy, 16 exhibited fluorescent contrast on their resected tissues (signal-to-background ratio: 1.94 ± 0.71). In contrast, tumors were identified in 3 of 10 specimens from patients who underwent preoperative chemotherapy (signal-to-background ratio: 1.63 ± 0.38). A total of 35 tissues were sampled from 30 specimens. Besides 30 tumor samples, 5 more suspicious samples with fluorescence signal were confirmed to be benign hemorrhagic tissues. Therefore, a sensitivity of 0.63 and a positive predictive value of 0.79 were achieved by the methylene blue fluorescence imaging strategy. Here, we demonstrate the feasibility of using methylene blue fluorescence imaging to identify breast cancer. Preoperative chemotherapy had an impact on imaging effect, which may reduce the detection rate. After all, methylene blue fluorescence imaging has great potential to be used into breast-conserving surgery for tumor-positive margins detection, but further clinical trial study is needed (http://www.chictr.org.cn/ Clinical Trial Registry ID: ChiCTR1800015400, Near-infrared fluorescence imaging applied in breast cancer identification with methylene blue).

Biophotonic technologies for assessment of breast tumor surgical margins—A review

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