higher than CT alone (92%, CI: 90–94%), but similar to morphological MRI (97%, CI: 97–98%) (Choi et al. 2010). A study comparing the evaluation of nodal metastases in uterine cancer patients by PET-CT and DW-MRI suggests that DW-MRI showed higher sensitivity but lower specificity than PET-CT; however, neither technique was sufficiently accurate to replace surgical lymphadenectomy (Kitajima et al. 2012). Similarly, a recent meta-analysis on the use of DW-MRI, PET or PET-CT, and CT for detecting lymph node metastases in patients with cervical cancer concludes that DW-MRI and PET or PET-CT are significantly better than CT; PET or PET-CT was associated with the highest specificity and DW-MRI with the highest sensitivity (Liu et al. 2017).

Concerning PET-MRI, sensitivity and specificity values above 90% have been reported by studies analyzing the nodal stage of cervical cancer patients; despite the high potential of this technique, further studies are needed before PET-MRI is established and integrated into clinical routine (Grueneisen et al. 2015; Kim et al. 2009).

Finally, we are not aware of any studies that analyze the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for detectingmetastaticlymphnodesin­gynecological cancer patients. However, there is some evidence indicating that DCE-MRI is useful to detect nodal involvement in patients with breast (Bahri et al. 2008; Loiselle et al. 2011), head and neck (Wendl et al. 2012; Yan et al. 2016), and prostate cancer (Lista et al. 2014). It is possible that similar results apply to corpus uteri and ovarian cancer patients as well; further studies are needed to address this knowledge gap.

3\ Technique

There is currently no consensus regarding the type of patient preparation before a pelvic MRI exam (Balleyguier et al. 2011). To limit bowel

motion artifacts 6 h of fasting before MRI (Engin 2006; Liu et al. 2009) or the intramuscular or intravenous injection of an antiperistaltic agent (Johnson et al. 2007) have been suggested. Antiperistaltic agents such as 1 mg glucagon (Glucagen®; Novo Nordisk, Bagsværd, Denmark) or 20 mg butyl-scopol- amine (Buscopan®; Boehringer Ingelheim GmbH, Ingelheim, Germany) seem to be most effective but are contraindicated in case of, e.g., diabetes or pheochromocytoma (Van Hoe et al. 1999). The urinary bladder should be moderately distended to avoid distortion of pelvic anatomy (Bourgioti et al. 2016).

3.1\ MRI

Lymph node assessment is included in the staging protocol of gynecological cancers (Balleyguier et al. 2011; Kinkel et al. 2009; Forstner et al. 2010). In cervical and endometrial cancer, the pelvis and retroperitoneum up to the level of the renal hilum should be covered. In vulvar and vaginal cancer, the inguinal lymph nodes have to be carefully assessed; in ovarian cancer, the pelvis, abdomen, and distal thorax should be analyzed for lymph node metastases.

Lymph nodes can be assessed on axial T2-weighted images. Additional three-dimen- sional T1and T2-weighted sequences with an isotropic voxel size of approximately 1 mm3 might be helpful to correctly evaluate lymph nodes which appear round in the axial plane but elongated or oval in additional planes. Further, 3D reconstructions might allow correct localization of nodes in relation to adjacent vessels and therefore improve guidance to suspicious nodes for the surgeon (Thoeny et al. 2014).

DW-MRI should be acquired with fat saturation to avoid that fatty hila around lymph nodes (generally considered to be a reliable criterion for benignity) lead to misleadingly low ADC measurements (Herneth et al. 2010). There is no

consensus­ regarding the optimal set of b-values to be acquired for diffusion-weighted imaging; commonly used values range between 500 and 1000 s/mm2 (in addition to a b = 0 s/mm2 scan) (Koplay et al. 2014; Thoeny et al. 2014, 2012; McVeigh et al. 2008). The reader should keep in mind that the computed ADC maps depend on the acquired b-values as well as on the hardware characteristics and field strength of the employed magnetic resonance scanner (Donati et al. 2014; Koc et al. 2012).

3.1.1\ Intravenous Unspecific Contrast Agents

There are no indications regarding the use of extracellular gadolinium-based contrast agents for lymph node imaging. On T1-weighted imaging, unspecific contrast agents might improve the differentiation of lymph nodes from vessels and facilitate the detection of necrotic lymph node regions.

The optimal time-point at which contrastenhanced images are acquired likely depends on the pathology at hand (Kinkel et al. 2009); however, imaging should be performed within 10 min of contrast medium injection to avoid diffusion into ascites (Forstner et al. 2010). 3D gradient echo MRI sequences might be preferable to standard 2D enhanced sequences as they allow the acquisition of relatively thin slices (e.g., 1 mm) with sufficient spatial resolution.

If the patient is pregnant or presents impaired renal function, the use of gadoliniumbased contrast agents needs to be carefully assessed (Thomsen et al. 2013) and might be substituted by thin-slice T2-weighted imaging and axial DW-MRI with fat saturation (Forstner et al. 2010).

3.1.2\ Intravenous Tissue-Specific Contrast Agents

Tissue-specific contrast agents that accumulate in healthy lymph node tissue could represent a valid additional tool for detecting metastatic lymph nodes. These contrast agents (e.g., feru-

moxtran-10; previously marketed as Sinerem® in Europe and as Combidex® in the United States) are based on ultrasmall superparamagnetic iron oxide particles (USPIO) with a diameter of approximately 20 nm. They are administered intravenously 24–36 h prior to imaging. Due to macrophage uptake, they cause healthy lymph nodes to appear hypointense on T2*-weighted MRI, whereas metastatic lymph nodes remain unchanged. Early studies suggest that ferumoxtran-10-based contrast agents improve the sensitivity of metastatic lymph node detection in endometrial and cervical cancer patients (Rockall et al. 2005) and considerably decrease the time needed by the radiologist to interpret the images (Thoeny et al. 2009). However, there are currently no USPIO-based contrast agents approved for differentiating metastatic from nonmetastatic lymph nodes on the market.

3.2\ CT

As lymph node assessment is an integral part of staging, the range of lymph nodes to be assessed is defined by the staging protocols of the different cancer types. CT imaging of gynecological cancer is usually performed with intravenous contrast medium; therefore, no special technique is necessary to assess lymph nodes. Multiplanar reconstructions facilitate the depiction of lymph nodes and their differentiation from bowel loops.

4\ Imaging Findings in Benign

and Malignant Lymph

Nodes: MRI/CT

On morphological images signs of nodal involvement include: a short axis diameter greater than 10 mm, visible necrosis (hyperintense foci on STIR or T2-weighted MRI), signal intensity similar to the primary tumor, and an irregular

nodal contour or tumor extending beyond the nodal capsule (Yang et al. 2000; Brown et al. 2003; Sala et al. 2010). However, these morphological features are rarely seen on CT or MRI. The contrast resolution of CT is too low to differentiate between normal and metastatic lymph node tissue. MRI generally has a higher soft tissue contrast resolution; however, the T1 and T2 relaxation times, as well as the proton densities, in lymphatic tissue and tumors are similar (Dooms et al. 1985).

To detect malignant lymph nodes, hyperintense noncontinuous round or oval structures on DW-MRI acquired with a high b-value (800– 1000 s/mm2) should be noted and correlated with morphological 3D images. Structures corresponding to lymph nodes warrant further assessment.

If a lymph node is associated with a hypointense structure on the respective ADC map and/ or on T2-weighted MRI, it is suspicious for malignancy. T1-weighted MRI should be employed to exclude that the low ADC is due to a fatty hilum. A short axis diameter greater than 10 mm, round shape, irregular or ill-defined border, and low signal intensity compared with muscle or groin lymph nodes on T2-weighted images are additional indicators of malignancy. On the contrary, eccentric fat and symmetric pelvic localization including similar shape and size on

axial reconstructed images support benignancy (Thoeny et al. 2014).

Figure 1 shows an example of a negative external iliac lymph node in a bilateral ovarian adenocarcinoma patient: despite appearing as a hyperintense structure on high b-value DW-MRI it presents an elongated and regular contour as well as a normal size on T1-weighted MRI. Figure 2 highlights a metastatic external iliac lymph node in a patient with high grade uterine leiomyosarcoma. The positive lymph node can be clearly identified as a round and enlarged structure which is hyperintense on high b-value DW-MRI and hypointense on the respective ADC map and on T2-weighted MRI. After 4 weeks of percutaneous radiotherapy the lymph node showed no clear response in size but ADC values increased from 0.8 to 1.6 × 10−3 mm2/s, corresponding to a favorable therapy response. Figure 3 illustrates an example of a cardiophrenic lymph node in a stage IIIC ovarian cancer patient which was suspicious for malignancy due to its hyperintense appearance on high b-value DW-MRI; however, its small size (short axis diameter less than 5 mm) on contrast-enhanced CT did not indicate malignancy (histopathological correlation is unavailable as this lymph node was not resected).

Efforts are underway to establish criteria that allow detecting pathologic cardiophrenic lymph

Fig. 1  A 53-year-old woman with bilateral ovarian adenocarcinoma with 16 histopathologic proven tumor-free pelvic lymph nodes. The arrow points to a negative external iliac lymph node with regular contour and normal size

on axial T1-weighted Dixon water sequence (a) and on diffusion-weighted MRI with body background suppression (b = 1000 s/mm2) (b)

Fig. 2  A metastatic external iliac lymph node of a 65-year-old woman with high grade uterine leiomyosarcoma on axial T2-weighted (a), diffusion-weighted (b = 800 s/mm2) MRI (b), and on the apparent diffusion coefficient map (c). After 4 weeks of percutaneous radio-

therapy the lymph node showed no clear response in size but increase of ADC values from 0.8 to 1.6 × 10−3 mm2/s diffusion-weighted MRI, (d), and corresponding ADC map, (e) corresponding to a favorable therapy response

nodes on CT. A recent study on 31 patients with advanced ovarian cancer suggests that a cut-off value of 7 mm on the short axis results in 63% sensitivity and 83% specificity. Figure 4 shows an example of enlarged, metastatic, cardiophrenic lymph nodes in a 61-year-old woman

diagnosed with FIGO IIIC high grade serous ovarian carcinoma 10 years ago. CT was performed recently due to upper right abdominal pain. Besides enlarged cardiophrenic lymph nodes, metastatic diaphragmatic, perihepatic, and pleural lesions were detected. Ovarian