Intraoperative near-infrared imaging of mesothelioma

Abstract

Though difficult to achieve, complete resection of malignant pleural mesothelioma is paramount to improving patient survival. Surgeons have traditionally been limited to using visual inspection and manual palpation to locate and remove cancerous tissue. However, intraoperative molecular imaging (IMI) is a promising new technology in surgery. Molecular imaging utilizes a fluorescent tracer that selectively accumulates in cancer cells. An imaging device is then used to detect and augment the fluorescent signal emitted from the fluorescent cancer cells. Our group and others have demonstrated that molecular imaging with either indocyanine green (ICG) or a folate receptor alpha (FRα) targeted fluorophore can accurately identify a number of intrathoracic malignancies. Early studies of intraoperative imaging have suggested its efficacy for malignant pleural mesothelioma. In a murine model of mesothelioma, intraoperative imaging was found to have sensitivity of 87% and specificity of 83%. In a pilot human study, eight patients with biopsy-proven epithelial malignant pleural mesothelioma were administered 5 mg/kg of intravenous ICG injection 24 h prior to resection. The following day, a near-infrared (NIR) imaging device was used to detect tumor fluorescence intraoperatively. After what was believed to be complete tumor excision, the wound bed was re-imaged for residual fluorescence indicative of retained tumor. When residual fluorescence was detected, additional tissue was resected, if feasible, and specimens were sent for pathologic correlation. In all cases, intraoperative fluorescence localized to mesothelioma deposits which were confirmed on final pathology. Following resection, fluorescence was confirmed ex vivo with a mean tumor-to-background ratio (TBR) of 3.2 (IQR: 2.9-3.4). It is hoped that this technology will improve outcomes for mesothelioma patients by allowing for a more complete oncologic resection.

Keywords: Intraoperative imaging; mesothelioma; surgical oncology.

Figure 1

Intraoperative NIR imaging of two mesothelioma deposits in a representative patient from the pilot human study. Preoperative CT scan is shown at left, followed by conventional thoracoscopic view in vivo, fluorescence imaging, and overlay of fluorescence imaging onto the brightfield view.

Figure 2

Back table ex vivo specimens resected from the same patient as described in Figure 1. Preoperative CT scan is shown at left, followed by brightfield imaging, fluorescence imaging, and overlay of fluorescence imaging onto the brightfield view.