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In vivo MR imaging of pelvic lymph nodes at ultra-high magnetic field (7T)
Tom Scheenen1,2, Bart Philips1, Rutger Stijns1, Ansje Fortuin1, Marloes Van Der Leest1, Mark Ladd3, Harald Quick2,4, Jelle Barentsz1, Stefan Rietsch2,4, Sacha Brunheim2,4, Stephan Orzada2, and Marnix Maas1

1Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, Netherlands, 2Erwin L Hahn Institute, Essen, Germany, 3German Cancer Research Center, Heidelberg, Germany, 4University Hospital Essen, Essen, Germany

Synopsis

The presence of metastases in pelvic lymph nodes marks the transition from local to systemic disease in many primary cancers in the lower abdomen. This crucial step in disease progression determines prognosis and the choice of treatment. Detection of metastatic lymph nodes is currently done with invasive diagnostic surgery, but could profit from USPIO-enhanced MRI. In this 7T study we present an in vivo anatomical baseline of number, size and location of visible lymph nodes in healthy volunteers, as well as the feasibility of using USPIO-enhanced MRI to detect suspicious lymph nodes in patients with prostate and rectal cancer.

Introduction

The presence of metastases of primary cancers in pelvic lymph nodes is a crucial step in disease progression1. Currently, staging of lymph nodes is performed with diagnostic lymph node dissections. A reliable non-invasive imaging method to detect metastases in pelvic lymph nodes would be of great benefit in the field of oncology. In the context of the ongoing debate2 on the validity and therapeutic effect of pelvic lymph node dissections, the current study was performed to: 1. Define an in vivo nodal anatomical baseline for validation of representative lymph node dissections and accompanying pathology reports, as well as for assessing a potential therapeutic effect of extended lymph node dissections. 2. Develop high resolution USPIO-enhanced MR imaging at ultra-high magnetic field strength (7T) to detect pelvic lymph node metastases in rectal and prostate cancer.

Methods

We used 2 static alternating RF shims at 7 Tesla for homogeneous pelvic imaging3 in 11 young healthy volunteers (mean age 31, range 25-39 years), 3 patients with prostate cancer and 3 patients with rectal cancer. The patients were measured 24-36 hours after administration of ferumoxtran-10 nanoparticles4 (USPIO) with a custom-made 8-channel TxRx body-array coil5. An advanced imaging protocol with water-selective iron-sensitive computed echo time (TE) imaging and lipid-selective imaging was developed6 to perform 3D MRI at a spatial resolution of 0.66x0.66x0.66mm3 to detect nodal structures in the pelvis. For water-selective imaging 5 echoes were acquired using a multi-gradient echo (mGRE) sequence from which, after fitting an exponential R2*-decay using a Weighted Linear Least Squares (WLLS) algorithm7, computed echo time images were reconstructed at various TEs. Number and short axis diameter of detected nodes (2 radiologists) in volunteers was measured and size distribution in each of six anatomical regions was assessed. An average volunteer-normalized nodal size distribution was determined. In patients, the T2* decay of the signal of lymph nodes was used to assess USPIO uptake: an indication of a normal functional lymph node.

Results

In total, 564 lymph nodes were detected in six pelvic regions of the 11 volunteers. The mean number was 51.3 lymph nodes per volunteer with a wide range of 19-91. Mean diameter was 2.3 mm with a range of 1 to 7 mm. 69% of the lymph nodes were 2 mm or smaller. The overall size distribution was very similar to the average volunteer-normalized nodal size distribution (Fig. 1). Most and on average largest lymph nodes were detected in the external iliac artery region (mean number 12.4, mean size 3.0 mm) and least as well as smallest lymph nodes were detected in the presacral region (mean number 5.9, mean size 1.7 mm) (Fig. 2).

Using the lipid series in patients, lymph nodes could be detected irrespective of the USPIO uptake. Normal lymph nodes with USPIO uptake appeared black on the computed TE imaging at TE=8 ms and had high R2* values, whereas suspicious lymph nodes without USPIO uptake had a high signal intensity with low R2* values. With extrapolation to TE=0 ms, the signal intensity of lymph nodes with USPIO uptake was recovered, such that computed TE imaging might also be useful for detecting normal lymph nodes (Fig. 3). In 4/6 patients, lymph nodes suspect for metastases down to 1.5 mm in short axis were detected in the iliac and mesorectal regions.

Discussion

The number of in vivo visible lymph nodes varies largely between subjects, whereas the normalized size distribution of nodes does not. The presence of many small lymph nodes (≤2 mm) in all anatomical regions in the pelvis renders representative or complete removal of pelvic lymph nodes extremely difficult. USPIO-enhanced MRI of the pelvis at 7 Tesla is feasible and offers opportunities for detecting very small lymph node metastases, due to its high intrinsic signal-to-noise ratio and high spatial resolution. This may enable more accurate pelvic lymph node staging of cancers in the lower abdomen than MR imaging at current clinical field strengths.

Conclusion

The value of extended lymph node dissections in the pelvis is under debate, both from a diagnostic perspective as well as from a treatment perspective. With this work, we could question the current validity of representative lymph node dissections and accompanying pathology reports by setting the in vivo nodal anatomical baseline in young volunteers. Moreover, we demonstrated the feasibility of performing USPIO-enhanced MRI of patients with prostate and rectal cancer at 7T.

Acknowledgements

No acknowledgement found.

References

  1. McMahon CJ, Rofsky NM, Pedrosa I (2010) Lymphatic metastases from pelvic tumors: anatomic classification, characterization, and staging. Radiology 254:31-46
  2. Fossati N, Willemse PM, van den Broeck T, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol. 2017;72(1):84-109.
  3. Orzada S, Maderwald S, Poser BA, Bitz AK, Quick HH, Ladd ME. RF excitation using time interleaved acquisition of modes (TIAMO) to address B1 inhomogeneity in high-field MRI. Magn Reson Med 2010;64(2):327-333.
  4. Fortuin AS, Bruggemann R, van der Linden J, et al. Ultra-small superparamagnetic iron oxides for metastatic lymph node detection: back on the block. Wiley interdisciplinary reviews Nanomedicine and nanobiotechnology 2018;10(1).
  5. Orzada S, Quick HH, Ladd ME, Bahr A, Bolz T, Yazdanbakhsh P, Solbach K, Bitz AK. A flexible 8-channel transmit/receive body coil for 7 T human imaging 2009; Honolulu, Hawaii, USA. p 2999.
  6. Philips BWJ, Fortuin AS, Orzada S, Scheenen TWJ, Maas MC. High resolution MR imaging of pelvic lymph nodes at 7 Tesla. Magn Reson Med 2017;78(3):1020-1028.
  7. Veraart J, Sijbers J, Sunaert S, Leemans A, Jeurissen B. Weighted linear least squares estimation of diffusion MRI parameters: strengths, limitations, and pitfalls. Neuroimage 2013;81:335-346.

Figures

Normalized size distribution of pelvic lymph nodes in 11 young volunteers

Mean number of lymph nodes over 11 volunteers per region in light blue, mean lymph node size in green.

Computed TE imaging at 7T of a patient with lymph node (LN) metastasized prostate cancer. (A-C) different computed TEs, (D) lipid selective imaging, (E) the original mGRE imaging at TE 7.24 ms, and (F) map of R2* relaxation rates. Three LNs with USPIO uptake (white circles) and one without (white arrow) were annotated. The signal decay of a normal LN with USPIO uptake(*) and a suspicious LN without uptake(#) are depicted in (H). The LN marked with (#) had an R2* value of 80s-1, whereas the LN marked with (*) showed fast T2* decay with an R2* value of 247s-1.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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