Synopsis

For patients with rectal cancer, the presence of lymph node metastases is an important risk factor for determining prognosis and stratifying for treatment. Clinically, lymph node staging is very challenging, especially when lymph nodes are small (<5mm). By using ultrasmall superparamagnetic iron oxide (USPIO) particles combined with (ultra) high magnetic field imaging (combidex-enhanced MRI), the detection rate of these metastatic lymph nodes may improve significantly. In this abstract we present the workflow for validating combidex-enhanced MRI by performing a node to node comparison of in vivo combidex-enhanced MRI findings with histopathological examination.

Introduction

The presence of lymph node metastases in rectal cancer is a key factor in determining an adequate treatment. Concluding on the lymph node status, however, is a major challenge.1 Ferumoxtran-10, an ultrasmall superparamagnetic iron oxide (USPIO) particle, has proven to be a valuable contrast agent for detecting lymph node metastases using MRI, also called combidex-enhanced MRI.2 Previous work showed that the diagnostic accuracy for the detection of small lymph node metastases (<5mm) dropped substantially.3 By using a 3 and 7 Tesla MRI scanner, it is possible to increase the spatial resolution of combidex-enhanced MRI, thereby increasing the sensitivity for the detection of small positive nodes.4 Histopathological validation of these nodes demands for a dedicated workflow from initial detection during in vivo MRI up to final histopathological examination. Here, we present the workflow and initial results in validating combidex-enhanced MRI for detecting small lymph node metastases in rectal cancer.

Methods

In this observational study, patients with biopsy proven rectal cancer are included 1-2 weeks prior to surgical treatment. Patients are administered with 2.6 mg/kg body weight of ferumoxtran-10 mixed with 0.9% saline solution. 24-36 hours later an MRI examination is performed at 3T and at 7T (Magnetom Prisma and 7T, Siemens Healthineers, Erlangen, Germany). The MR protocol and parameters are displayed in Table 1.5 The detection of the lymph nodes is done on lipid-selective T1-weighted gradient echo MR images and the suspicion on metastatic manifestation is determined on T2*-weighted images6. Surgical treatment consists of a total mesorectal excision, in which the rectum including surrounding fatty tissue with lymph nodes is removed. After fixation in formalin, the surgical specimen is examined on a 7 Tesla preclinical MR system (ClinScan, Bruker® BioSpin, Ettlingen, Germany). These ex vivo MR images are used to annotate lymph nodes for an MR-guided pathological examination. The annotations enable a node-to-node comparison between in vivo MRI and pathology. The histopathological analysis is then used to validate the results of the 3T and 7T MRI scans. A complete overview of the workflow is given in Figure 1.

Results

Three patients have been included in this ongoing study. Two patients underwent 3T MRI and 7T MRI and one patient underwent 3T MRI only. Two patients were scheduled for direct surgical treatment and one patient had received preoperative chemoradiotherapy. In these three patients 9 lymph nodes were considered malignant with a mean diameter of 4.1 mm (range 2 - 5 mm, example shown in Figure 2). The 7T ex vivo MRI scans revealed 146 lymph nodes with a mean diameter of 2.7 mm (range 0.8 – 5.2 mm). Histopathological examination harvested 48 lymph nodes from the surgical specimens, including the 9 lymph nodes suspicious for metastases based on combidex-enhanced MRI. 8 out of 9 suspicious nodes could be matched to histology as visualized in Figure 3.

Discussion

The preliminary data of the ongoing study shows that it is feasible to visualize potentially malignant lymph nodes in rectal cancer patients by using combidex-enhanced MRI. Both 3T and 7T MRI showed that the contrast agent can migrate to lymph nodes after an intravenous infusion. Preoperative chemoradiotherapy may impede the transport of the nano-particles towards the locoregional lymph nodes, which has to be explored in future patients. By using our current workflow, we are able to identify the potentially metastatic lymph nodes at initial in vivo MRI and keep track of them all the way to the histological slide at pathology. The additional step of the 7T ex vivo MRI scan allows the node-to-node correlation between the in vivo MRI images and histology. This extra step in the workflow is of great value in determining the accuracy of combidex-enhanced MRI on a lymph node basis. The lymph nodes with a high suspicion of malignancy can be identified ex vivo and pointed out during work-up for histological examination, thereby enabling the pathologist to make a final statement on the lymphatic spread of the cancer and on the predictive value of combidex-enhanced MRI for rectal cancer staging.

Acknowledgements

No acknowledgement found.

References

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