Abstract

Abstract Background Extensive lymph node dissections during esophagectomy may be omitted in patients with esophageal cancer without lymph node metastases, reducing associated morbidity. A promising technique to detect lymph node metastases is MRI with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, ferumoxtran-10). To validate USPIO-enhanced MRI in patients with esophageal cancer, a framework is designed to compare lymph nodes of the MRI scans with histopathology data on a node-to-node level. Methods USPIO-nanoparticles are intravenously infused 24 to 36 hours before MRI. USPIO-enhanced MRI is performed before and after nCRT. After nCRT, patients are scanned under general anesthesia immediately prior to surgery in the MR system of the hybrid MITeC operation room with controlled mechanical ventilation. During controlled prolonged apneu, a four-minute iron-sensitive MRI acquisition is used to visualize suspicious esophageal lymph nodes without motion artefacts. Resected specimens, still containing USPIO, are measured ex-vivo in a preclinical 7T MR system before histopathological examination. A radiological assessment of the presence of suspicious lymph nodes in-vivo is matched to the ex-vivo nodes on preclinical MRI, providing the ground truth for the presence of metastases. Results Currently, five patients have completed the full study protocol. Two patients underwent the first UPSIO-MRI but did not undergo surgery due to progressive disease. First results show that MRI under anesthesia prior to surgery with controlled mechanical ventilation was possible resulting in a clinically relevant spatial resolution to visualize possibly malignant lymph nodes. In these five patients, the radiologist found 58 lymph nodes with a mean diameter of 8.4 mm before nCRT and 40 lymph nodes with a mean diameter of 7.4 mm after nCRT. In total, 126 lymph nodes were analyzed by histopathology. Suspicious nodes were identified and could be matched using corresponding anatomical landmarks to the ex-vivo MRI, which showed good visual agreement with esophageal specimen after resection. Conclusions We performed USPIO-enhanced MRI in patients with esophageal cancer and proposed a method to validate USPIO-enhanced MRI to detect suspicious lymph nodes in these patients. Results on the feasibility of USPIO-enhanced MRI to detect metastatic lymph nodes after nCRT are still awaited.

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