Synopsis

Metastatic nodes in prostate cancer are associated with poor prognosis. Conventional MRI, relying on short-axis diameter (SAD) suffers from poor accuracy in identifying metastatic nodes. In this study, we compare fat fraction signal from MRI mDixon acquisitions (FF) with apparent diffusion coefficients of nodes and quantitative contrast-enhanced two-point mDixon T1 images (CE-mDixon), in discriminating between benign and metastatic nodes using 18F-Choline PET-CT as reference standard. We showed that FF and CE-mDixon discriminate benign from involved lymph nodes that are small in size unlike SAD or ADC of nodes; FF, not necessitating contrast agents, holds promise as a clinical tool.

Introduction

Identifying metastatic nodes in prostate cancer patients is essential as lymph node involvement is associated with poor prognosis (1). Conventional MRI, relying on morphological aspects of nodes, particularly short-axis diameter (SAD) as a measure of size, or the ratio of short-to-long axis diameter (SAD/LAD) as a measure of shape, to discriminate between normal and metastatic nodes, suffers from poor accuracy (2, 3). Apparent diffusion coefficient (ADC) of nodes in MRI has been previously assessed with conflicting accuracy results (4-7). Qualitative assessment of the absence of a fatty hilum in involved nodes may be useful (8) but quantitative MRI fat measurements data are lacking as well as quantitative contrast-enhanced MRI characteristics which may improve staging performance.

In a previous pilot study, we demonstrated that quantitative MRI mDixon signal fat fraction (FF) measurements calculated from ROI signal intensity (SI) as SIfat / (SIwater + SIfat), in pelvic lymph nodes may discriminate involved and benign nodes using 18F-Choline PET-CT as a reference standard (9). To consolidate this finding, we also showed that FF in pelvic lymph nodes are highly repeatable in healthy volunteers with very similar mean FF values between scan and rescan MRI studies (10). In this study, we aimed to compare mDixon FF with apparent diffusion coefficient (ADC), mean signal intensity (mSI) of contrast-enhanced T1W two-point mDixon imaging and with morphological parameters of nodes such as SAD and SAD/LAD to discriminate between benign and involved nodes in prostate cancer patients.

Methods

FF was analysed from a dataset of intermediate and high-risk biopsy-proven prostate cancer patients who underwent both whole-body MRI (as per MRI protocol in Table 1) and 18F-fluorocholine PET-CT from vertex to mid-thigh as per institutional protocol (11). Eleven patients [median age of 64 years (range 61-72) and median PSA of 60.0 (range 37-170)] were identified.

A board-certified radiologist blinded to clinical and 18F-fluorocholine PET-CT data, manually contoured normal and abnormal nodes on MRI considering each of the following pelvic node stations: para-aortic, common iliac, proximal internal iliac, external iliac, obturator, pre-sacral and inguinal. Nodes were drawn on T2-weighted images and correspondingly on pre-and post-contrast two-point mDixon sequences and ADC maps (derived from diffusion-weighted b-values of 0,100, 300 and 1000 mm/s2).

Forty-three nodes were contoured and the following metrics were obtained for each node: SAD, SAD/LAD, mean T2 signal intensity (SI) normalised to the bladder (nT2SI)(12), mean ADC, mean FF, mean SI on contrast-enhanced mDixon in-phase (CE-IP) and out-of-phase (CE-OP). The nodes were divided into PET positive and PET negative groups according to reference standard 18F-fluorocholine PET-CT.

Each parameter was compared between the two groups using unpaired t-test with Welch’s correction. Only nodes with SAD<15mm were analysed for quantitative MRI parameters (13).

Results

Discussion

Our study shows that FF of nodes can distinguish pathological nodes from normal ones unlike short-axis diameter, ratio of short-to-long axis measurements or ADC values. Involved nodes show enhancement on CE-OP mDixon images with statistically higher mean signal intensities than benign nodes.

Our findings are in accordance with previous studies demonstrating the poor discriminating performance of nodal size (2) or shape and ADC of in metastatic pelvic nodes (6). Overlap of ADC values in benign and malignant nodes could be due to the small-sized nodes. However, the decreasing quantitative FF in involved nodes is in keeping with the qualitative description of the loss of a fatty hilum in pathological nodes described in other cancers (14, 15). We have also shown that involved nodes show enhancement on CE-OP mDixon. Whilst this necessitates the use contrast agent, FF measurement confers the advantage of not using any.

Conclusion

Acknowledgements

This research was supported by grants the Comprehensive Cancer Imaging Centre, the UCLH Biomedical Research Centre, Prostate Cancer UK and London Cancer Alliance.

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