USPIO-enhanced MRI of pelvic lymph nodes at 7-T: preliminary experience.

PURPOSE: To evaluate the technical feasibility of high-resolution USPIO-enhanced magnetic resonance imaging of pelvic lymph nodes (LNs) at ultrahigh magnetic field strength. MATERIALS AND METHODS: The ethics review board approved this study and written informed consent was obtained from all patients. Three patients with rectal cancer and three selected patients with (recurrent) prostate cancer were examined at 7-T 24-36 h after intravenous ferumoxtran-10 administration; rectal cancer patients also received a 3-T MRI. Pelvic LN imaging was performed using the TIAMO technique in combination with water-selective multi-GRE imaging and lipid-selective GRE imaging with a spatial resolution of 0.66 × 0.66 × 0.66mm3. T2*-weighted images of the water-selective imaging were computed from the multi-GRE images at TE = 0, 8, and 14 ms and used for the assessment of USPIO uptake. RESULTS: High-resolution 7-T MR gradient-echo imaging was obtained robustly in all patients without suffering from RF-related signal voids. USPIO signal decay in LNs was visualized using computed TE imaging at TE = 8 ms and an R2* map derived from water-selective imaging. Anatomically, LNs were identified on a combined reading of computed TE = 0 ms images from water-selective scans and images from lipid-selective scans. A range of 3-48 LNs without USPIO signal decay was found per patient. These LNs showed high signal intensity on computed TE = 8 and 14 ms imaging and low R2* (corresponding to high T2*) values on the R2* map. CONCLUSION: USPIO-enhanced MRI of the pelvis at 7-T is technically feasible and offers opportunities for detecting USPIO uptake in normal-sized LNs, due to its high intrinsic signal-to-noise ratio and spatial resolution. KEY POINTS: • USPIO-enhanced MRI at 7-T can indicate USPIO uptake in lymph nodes based on computed TE images. • Our method promises a high spatial resolution for pelvic lymph node imaging.

High resolution MR imaging of pelvic lymph nodes at 7 Tesla.

PURPOSE: Pelvic lymph node (PLN) metastases are often smaller than 5 mm and difficult to detect. This work presents a method to perform PLN imaging with ultrahigh-field MRI, using spectrally selective excitation to acquire water and lipid-selective imaging at high spatial resolution. METHODS: A 3D water-selective multigradient echo (mGRE) sequence and lipid-selective gradient echo (GRE) sequence were tested in six healthy volunteers on a 7 Tesla (T) MRI system, using time interleaved acquisition of modes (TIAMO) to improve image homogeneity. The size distribution of the first 10 iliac PLNs detected in each volunteer was determined, and the contrast-to-noise ratio (CNR) of these lymph nodes (LNs) was compared with the individual mGRE images, sum-of-squares echo addition, and computed T2*-weighted images derived from the T2* fits. RESULTS: LN imaging was acquired robustly at ultrahigh field with high resolution and homogeneous lipid or water-selective contrast. PLNs down to 1.5-mm short axis were detected with mean ± standard error of the mean (SEM) short and long axes of 2.2 ± 0.1 and 3.7 ± 0.2 mm, respectively. Computed T2*-weighted imaging allowed flexibility in T2* contrast while featuring a CNR up to 90% of the sum-of-squares echo addition. CONCLUSION: Ultrahigh-field MRI in combination with TIAMO and frequency-selective excitation enables high-resolution, large field-of-view MRI of the lower abdomen, and may ultimately be suitable for detecting small PLN metastases. Magn Reson Med 78:1020-1028, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Lymphotropic nanoparticle-enhanced MRI in prostate cancer: value and therapeutic potential.

Nodal staging in prostate cancer is suboptimal both with respect to current imaging modalities and pelvic lymph node dissection, and thus other techniques are being explored. Lymphotropic nanoparticle-enhanced MRI, also called magnetic resonance lymphography (MRL), is a technique that has shown high sensitivity (65-92 %) and excellent specificity (93-98 %) in detecting prostate cancer lymph node metastases. This technique aids in the detection of metastases in non-enlarged small nodes. MRL has been useful in determining the location and pathways of spread in nodal chains. Knowledge of the location of lymph node involvement is important for decisions regarding appropriate therapeutic options, such as image-guided therapy.. A geographic miss in radiotherapy can be avoided with the use of MRL-guided focal therapy. This paper provides an overview of current literature, lessons learned, and new therapeutic options with nanoparticle-enhanced MRI.

The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

BACKGROUND: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. PURPOSE: The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. MATERIALS AND METHODS: Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. RESULTS: At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. CONCLUSIONS: In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

Magnetic resonance imaging at ultra-high magnetic field strength: An in vivo assessment of number, size and distribution of pelvic lymph nodes.

OBJECTIVE: The definition of an in vivo nodal anatomical baseline is crucial for validation of representative lymph node dissections and accompanying pathology reports of pelvic cancers, as well as for assessing a potential therapeutic effect of extended lymph node dissections. Therefore the number, size and distribution of lymph nodes in the pelvis were assessed with high-resolution, large field-of-view, 7 Tesla (T) magnetic resonance imaging (MRI) with frequency-selective excitation. MATERIALS AND METHODS: We used 7 T MRI for homogeneous pelvic imaging in 11 young healthy volunteers. Frequency-selective imaging of water and lipids was performed to detect nodal structures in the pelvis. Number and size of detected nodes was measured and size distribution per region was assessed. An average volunteer-normalized nodal size distribution was determined. RESULTS: In total, 564 lymph nodes were detected in six pelvic regions. Mean number was 51.3 with a wide range of 19-91 lymph nodes per volunteer. Mean diameter was 2.3 mm with a range of 1 to 7 mm. 69% Was 2 mm or smaller. The overall size distribution was very similar to the average volunteer-normalized nodal size distribution. CONCLUSIONS: The amount 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 (≤2mm) renders representative or complete removal of pelvic lymph nodes to be very difficult. 7T MRI may shift the in vivo detection limits of lymph node metastases in the future.

Ultra-small superparamagnetic iron oxides for metastatic lymph node detection: back on the block.

In the past 15 years, encouraging clinical results for the detection of small lymph node metastases was obtained by the use of Combidex-enhanced MRI (CEM, also known as magnetic resonance lymphography). Withdrawal of the European Medicines Agency approval application by the manufacturer made it impossible for patients to benefit from this agent; a loss, especially for men with prostate cancer. Current conventional imaging techniques are not as accurate as CEM is, thus a surgical diagnostic exploration (extended lymph node dissection) is still the preferred technique to evaluate the lymph nodes, resulting in peri- and postoperative complications. In 2013, the Radboud University Medical Center (Radboudumc) obtained all licenses and documentation for the production process of Combidex (ferumoxtran-10), and manufactured the contrast agent under supervision of the Department of Pharmacy. Since 2014, 310 men with prostate cancer have been examined with CEM in the Radboudumc. Within this cohort, seven minor possibly contrast-related adverse effects were observed after administration of Combidex. As the contrast agent is now back again in the Netherlands, this review highlights the working mechanism, previous results, observed side effects since the reintroduction, and the future perspectives for Combidex. WIREs Nanomed Nanobiotechnol 2018, 10:e1471. doi: 10.1002/wnan.1471 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Intranodal signal suppression in pelvic MR lymphography of prostate cancer patients: a quantitative comparison of ferumoxtran-10 and ferumoxytol.

OBJECTIVES: The key to MR lymphography is suppression of T2* MR signal in normal lymph nodes, while retaining high signal in metastatic nodes. Our objective is to quantitatively compare the ability of ferumoxtran-10 and ferumoxytol to suppress the MR signal in normal pelvic lymph nodes. METHODS: In 2010, a set of consecutive patients who underwent intravenous MR Lymphography (MRL) were included. Signal suppression in normal lymph nodes in T2*-weighted images due to uptake of USPIO (Ultra-Small Superparamagnetic Particles of Iron Oxide) was quantified. Signal suppression by two USPIO contrast agents, ferumoxtran-10 and ferumoxytol was compared using Wilcoxon's signed rank test. RESULTS: Forty-four patients were included, of which all 44 had a ferumoxtran-10 MRL and 4 had additionally a ferumoxytol MRL. A total of 684 lymph nodes were identified in the images, of which 174 had been diagnosed as metastatic. USPIO-induced signal suppression in normal lymph nodes was significantly stronger in ferumoxtran-10 MRL than in ferumoxytol MRL (p < 0.005). CONCLUSIONS: T2* signal suppression in normal pelvic lymph nodes is significantly stronger with ferumoxtran-10 than with ferumoxytol, which may affect diagnostic accuracy.

Geographical distribution of lymph node metastases on MR lymphography in prostate cancer patients.

PURPOSE: To investigate the pattern of lymph node spread on magnetic resonance lymphography (MRL) in prostate cancer patients and compare this pattern to the clinical target volume for elective pelvis irradiation as defined by the radiation therapy oncology group (RTOG-CTV). METHODS AND MATERIALS: The charts of 60 intermediate and high risk prostate cancer patients with non-enlarged positive lymph nodes on MRL were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines for delineation of the RTOG-CTV. Five lymph node regions outside this RTOG-CTV were defined: the para-aortal, proximal common iliac, pararectal, paravesical and inguinal region. RESULTS: Fifty-three percent of the patients had an MRL-positive lymph node in a lymph node region outside the RTOG-CTV. The most frequently involved aberrant sites were the proximal common iliac, the pararectal and para-aortal region, which were affected in 30%, 25% and 18% respectively. CONCLUSION: More than half of the patients had an MRL-positive lymph node outside the RTOG-CTV. To reduce geographical miss while minimizing the toxicity of radiotherapy, image based definition of an individual target volume seems to be necessary.

Value of PET/CT and MR lymphography in treatment of prostate cancer patients with lymph node metastases.

PURPOSE: To determine the clinical value of two novel molecular imaging techniques: (11)C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. METHODS AND MATERIALS: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined. The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. RESULTS: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. CONCLUSION: In patients with PCa, both molecular imaging techniques, MRL and (11)C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases.

Comparison of nodal risk formula and MR lymphography for predicting lymph node involvement in prostate cancer.

PURPOSE: To compare the nodal risk formula (NRF) as a predictor for lymph node (LN) metastasis in patients with prostate cancer with magnetic resonance lymphography (MRL) using Ultrasmall Super-Paramagnetic particles of Iron Oxide (USPIO) and with histology as gold standard. METHODS AND MATERIALS: Logistic regression analysis was performed with the results of histopathological evaluation of the LN as dependent variable and the nodal risk according to the NRF and the result of MRL as independent input variables. Receiver operating characteristic (ROC) analysis was performed to assess the performance of the models. RESULTS: The analysis included 375 patients. In the single-predictor regression models, the NRF and MRL results were both significantly (p<0.001) predictive of the presence of LN metastasis. In the models with both predictors included, NRF was nonsignificant (p=0.126), but MRL remained significant (p<0.001). For NRF, sensitivity was 0.79 and specificity was 0.38; for MRL, sensitivity was 0.82 and specificity was 0.93. After a negative MRL result, the probability of LN metastasis is 4% regardless of the NRF result. After a positive MRL, the probability of having LN metastasis is 68%. CONCLUSIONS: MRL is a better predictor of the presence of LN metastasis than NRF. Using only the NRF can lead to a significant overtreatment on the pelvic LN by radiation therapy. When the MRL result is available, the NRF is no longer of added value.