Introduction

Pelvic lymph node (LN) metastasis is an important prognostic factor in all male and female malignant urogenital neoplasms. Prior to surgery, familiarity with the lymphatic drainage pathways and accurate mapping of positive LNs may reduce the postoperative recurrence and prolong survival, as well as decrease the morbidity and mortality caused by the gold standard, pelvic LN dissection. In this article, we describe the primary lymphatic drainage pathway for common pelvic urogenital malignancies and summarize the common imaging characteristics of pelvic metastatic LNs as well as some emerging imaging technologies in this field.

Pelvic Lymphatic Drainage Pathways

General Pelvic Lymphatic Spread

The lymphatic drainage patterns of urogenital malignancies are complex in the pelvis. The metastases usually involve specific sentinel lymph nodes (SLNs) along the supply or drainage vessels of the organs with primary tumors. This is followed by further spread to the next LN station. Skip metastases of LN seldom occur in urogenital tumors. There are four main pathways of pelvic LNs (Fig. 1): (1) the anterior route, which drains lymph from the anterior wall of the bladder along the umbilical artery to the internal iliac (hypogastric) nodes; (2) the lateral route, which drains lymph from the pelvic organs to the medial chain of the external iliac nodal group (obturator LNs); (3) the hypogastric route, which drains along the visceral branches of the hypogastric vessels to the junctional nodes located between the internal and external iliac vessels; (4) the presacral route, which includes the LNs anterior to the sacrum and coccyx [1••]. Among them, the lateral route is the most common pathway, and the anterior route is the rarest.

Fig. 1
figure 1

Anatomical location of pelvic lymph nodes. a Anterior view. b Lateral view

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Prostate Cancer

The survival rate of patients with prostate cancer correlates with LN metastasis, with a 5-year tumor-free survival rate of 85 % for pN0 disease decreasing to approximately 50 % for pN1 disease [2]. The lymphatic drainage of prostate cancer (Fig. 2a) mainly spreads along the lateral route to the obturator LNs, the most common SLNs (up to 60 %), from which the metastases spread to the middle and lateral external iliac LNs. Besides, the junctional nodes belonging to the hypogastric lymph group are also commonly involved because of the hypogastric route. Metastatic nodes in the presacral region are relatively rare [3]. Mattei and colleagues provided a detailed SLN map of the prostate using a multimodality technique [including SPECT/CT, SPECT/MRI, and ultrasound-guided intraprostatic injection of technetium (Tc-99m) nanocolloid]. They observed the SLN distribution as follows: external iliac and obturator fossa (37.9 %), internal iliac (22.6 %), presacral and pararectal (8.2 %), common iliac (15.8 %), para-aortic/paracaval (12.0 %), and inguinal (0.6 %) [4•]. The study by Weckermann et al. obtained similar results. They found 86 % positive pelvic nodes distributed in the internal iliac (35 %), external iliac (26 %), and obturator (25 %) regions followed by the presacral (9 %), common iliac (3 %), and aortic bifurcation (1 %) regions. These data evidenced that quite a few metastatic pelvic lymph nodes are located outside the template area (external iliac, obturator fossa, and internal iliac regions) of standard pelvic lymphadenectomy. The missed rate of standard dissection reached up to 63 %, mainly contributed by presacral, common iliac, and retroperitoneal LNs [5]. Most of the prostate studies supported that there was no skip metastasis to the second level region (the common iliac and retroperitoneal LNs) if the first level region (the obturator, external and internal iliac, and presacral LNs) was negative, although up to 15 % of positive nodes were detected in the aorta and vena cava regions [6, 7].

Fig. 2
figure 2

The illustrations of specific lymphatic drainage pathways of pelvic tumors

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Cervical Cancer

The stages of cervical cancer are positively correlated with the LN status. From stage IA, IB, IIA, and IIB, the metastatic rates of lymph nodes are 0–8, 0–17, 12–27, and 25–39 %, respectively [8]. However, LN metastasis to the pelvic and para-aortic regions cannot alter the FIGO staging, only influencing the prognosis [9]. In locally advanced cervical cancer, the 5-year survival rate decreases from 57 % in patients without LN involvement to 34 % in those with positive pelvic nodes and 12 % in those with positive para-aortic nodes [10]. Lymphatic metastases in cervical cancer depend on three main routes (Fig. 2b): the lateral route is the main one, which spreads through the lateral parametrium and drains to the external iliac, internal iliac, and gluteal LNs; the anterior route is next, which drains along the vesicouterine ligament to internal iliac LNs; the posterior route, which drains along the sacrouterine ligament and the ureter to the presacral, common iliac, and para-aortic LNs, is rarely observed [11]. As a midline structure, the lymphatic drainage of the cervix can spread to the bilateral pelvic regions. The SLNs are distributed in seven retroperitoneal groups (paracaval, precaval, retrocaval, intercavoaortic, preaortic, paraaortic, retroaortic) and eight pelvic regions (deep and superficial common iliac, external iliac, deep and superficial obturator, internal iliac, presacral, parametric) [12•]. In early cervical cancer, the obturator nodes are the most common SLNs, which combined with external iliac nodes could comprise over 75 % of all SLNs [13]. Rob et al. also identified the positive SLN distribution to be 45.5 % supra-obturator nodes and 38.6 % external iliac nodes, followed by 6.8 % bifurcation and common iliac nodes, 4.5 % presacral nodes, and 4.5 % the medial part of the lateral parametrium [14]. An extremely close correlation between parametrial involvement and positive pelvic nodes was demonstrated by Benedetti-Panici et al. [15]. Just like in prostate cancer, common iliac, para-aortic, and inguinafemoral LNs are commonly seen as secondary metastatic sites in cervical cancer, while skip metastasis to para-aortic LNs is only reported in <1 % cases [16].

Bladder Cancer

The survival time of bladder cancer is negatively correlated with the number and size of the involved nodes, and it declines with capsular penetration of the nodes [17, 18]. The classic lymphatic channels of the bladder first spread to the perivesical LNs and then reach the other primary nodal basins in the iliac and presacral regions [19]. The obturator and internal iliac nodes are the most common SLNs [20]. The lymphatic landing site varies by the bladder tumor locations (Fig. 2c). Lymphatic metastasis from tumors in the superolateral wall commonly spreads to external iliac LNs, whereas those from the anterior wall, fundus, and neck tend to involve internal iliac LNs. Besides, a few sacral nodes can be directly involved by tumors in the neck and trigone [21••]. All three LN groups can further spread upward to the bilateral common iliac and para-aortic regions, especially in patients with higher T stage tumors [22]. In a multicenter study, Leissner et al. identified the metastatic LN distribution in bladder cancer as follows: 14.1 and 6.9 % right and left obturator spaces, 11.0 and 8.1 % right and left deep obturator spaces, 6.7 and 7.0 % right and left lateral to external iliac artery, 6.3 % both the right and left lateral to common iliac artery, 6.0 % presacral, and 12.9 % retroperitoneal [23]. Abol-Enein et al. also supported the obturator LNs as the most common positive SLNs of bladder tumors. They also pointed out that skip metastasis might not exist in bladder cancer since isolated extrapelvic nodal disease was not detected. Bilateral nodal involvement is common and occurred in approximately 39 % of bladder cancers, even if the primary lesion was limited to the unilateral wall of the bladder [20]. Based on this, both Abol-Enein and Leissner emphasized the need to promote bilateral lymphadenectomies.

Endometrial Cancer

The prognosis of endometrial cancer is strongly impacted by pelvic LN metastases [24], with a 5-year recurrence-free survival of 90 % in patients without LN involvement versus 75 % in those with positive pelvic LNs and 38 % in those with positive para-aortic LNs [25]. Three main paths of lymphatic spread of the uterine corpus have been described, as shown in Fig. 2d: the most common route drains through the hypogastic or obturator regions to the common iliac LNs; next, spreading along the round ligament to the inguinal LNs takes place; the last directly involves the para-aortic LNs through the ovarian vessels. The external iliac and obturator nodes are most commonly affected in endometrial cancer [26, 27•]. When the tumor is confined to the corpus, isolated positive LNs spread to the external iliac and obturator regions more frequently, while if the cervical area is invaded, the external and common iliac regions are more common [27•]. Although direct lymphatic drainage to the para-aortic region is more commonly detected in endometrial cancer confined to the corpus than in tumors invading the cervix [27•, 28], most of involved para-aortic nodes are associated with the presence of pelvic nodal metastasis, especially positive obturator nodes [27•].

Ovarian Cancer

The incidence of LN metastasis of ovarian cancer largely depends on the histological subtypes and grades of primary tumors. In a systematic review, Kleppe et al. concluded LN metastasis was absent in clinical stage I–II sex cord stromal tumors, but present in as much as 11 and 18.1 %, respectively, in stage I–II malignant germ cell tumors and dysgerminoma of the ovary [29]. Moreover, from grade 1 to 3, the incidence rate of LN metastasis increased from 4.0 to 20.0 % [30]. The lymphatic spread of ovarian cancer may take two main pathways (Fig. 2e): one follows the broad ligament to the internal iliac, external iliac, and obturator LNs; another one drains along the infundibulopelvic ligament to the aortic LNs [31•]. Therefore, both pelvic and para-aortic LNs could be primary metastatic SLNs of ovarian cancers. There is a third uncertain route, which spreads through the bilateral round ligament of the uterus to the external iliac and deep inguinal LNs [32]. The involved LNs are most frequently detected in the para-aortic region (83 %), followed by the external iliac region (59 %) and obturator region (53 %) [33]. Both unilateral and bilateral ovarian tumors can involve bilateral pelvic LNs. Cass et al. observed isolated ipsilateral, isolated contralateral, and bilateral node metastases comprised 50 % (5/10), 30 % (3/10), and 20 % (2/10), respectively [34].

Vaginal Cancer

In traditional opinions, the lymphatic drainage of vaginal cancer depends on the locations of the primary tumors. Similarly to cervical cancer, nodal metastasis of upper tumors usually extends to deep pelvic (including internal and external iliac and obturator nodes) and para-aortic LNs, while lower tumors are more likely to involve the inguinofemoral triangle than vulvar cancer (Fig. 2f). However, recent studies demonstrated LN metastases did not follow the traditional routes so exactly. Frumovitz et al. noted 55.6 % (5/9) of patients with vaginal cancer present positive nodes in unexpected regions. Three patients with lower tumors had an SLN in the pelvis, and two patients with upper tumors had an SLN in the inguinal triangle [35].

Rectal Cancer

As intraoperative assessment of the LN status by the surgeon is not reliable [36] and SLN biopsy is not as valuable as its application in other tumors [37], understanding the lymphatic drainage patterns of rectal cancer is essential to correctly estimate pelvic node status and decrease the postoperative recurrence rate. The lymphatic extension of rectal cancer is mainly based on two pathways (Fig. 2g): one is the superior route, spreading along the superior rectal artery to the root of the inferior mesenteric artery; another is the lateral route, spreading along the middle rectal and pudendal arteries to the root of the internal iliac artery [38–40]. There is a correlation between the locations of tumors [upper, above the peritoneal reflection (PR); lower, below the PR; middle, at the level of the PR] and the patterns of LN metastasis. Compared with tumors above the PR, tumors below the PR have more nodal metastases and a greater tendency to spread to the bilateral pelvic nodes through the lateral pathway [41•]. Besides, the pathohistological characteristcs of primary tumors, including the tumor size, depth of bowel wall invasion, number of positive mesorectal nodes, differention type, and lymphatic and venous invasion, also impact pelvic nodal metastasis [38, 39, 41]. The most common positive pelvic LNs in lower recal cancer are in the middle rectal root region (19 %) followed by the internal iliac region (9 %), obturator region (9 %), external iliac region (7 %), and common iliac region (4 %) [38, 39].

Imaging Methods

Common imaging modalities for assessment of pelvic LNs are mainly classified into three divisions: first, conventional cross-sectional imaging, including computed tomography (CT) and magnetic resonance imaging (MRI); second, functional imaging, including functional MRI (fMRI), lymphotropic MR contrast, position emission tomography/CT (MRI) [PET/CT (MRI)], and single photon emission computed tomography/CT (MRI) lymphoscintigraphy (SPECT/CT (MRI) LSG); third, interstitial CT (MRI) lymphography (ICTLG or IMRILG). In addition, there are some emerging modalities, such as photoacoustic technology and nanotechnology, that also display potential in the detection of pelvic nodal LN metastases.

Conventional Cross-Sectional Imaging

CT

CT is one of the most widely used imaging modalities in the evaluation of pelvic LN status. Various CT appearances have been adopted as diagnostic standards, alone or in combination, for assuring accuracy in differentiating between benign and malignant LNs. These LN features include the size, shape, border, margin, extracapsular invasion, intranodal texture, patterns, and degree of enhancement; of these, size is still the preferred one despite the low sensitivity reported by many studies [42, 43]. The size threshold of pelvic LNs ranges from 0.5 to 2 cm [44, 45]. A short axis diameter above 1 cm with an oval shape or 0.8 cm with a round shape is generally accepted as the criterion for metastasis [43, 46]. With this criterion, the specificity for detecting positive pelvic LN on CT reached 97 %, but the sensitivity was only 34 % [47]. The low sensitivity is due to false-positive cases caused by hypoplasia and enlargement of LNs associated with local inflammation as well as false-negative cases due to micrometastases (smaller than 2 mm) hiding in nodes of normal size (short diameter less than 10 mm) [48]. This phenomenon was proved by studies on prostate and cervical cancers. It is more common in the pelvic than retroperitoneal region [49–51]. Necrosis and calcification within the nodes are considered specific CT signs of metastatic nodes, especially with the same manifestations in primary tumors. Necrotic LNs frequently occur in cervical cancer and bladder cancer [21, 52], while calcification can be noted in ovarian cancers [53]. However, these features should be cautiously discriminated from other benign statuses, such as necrotizing lymphadenitis and tuberculosis. Moreover, the sensitivity of necrosis (27 %) is even lower than size despite the high PPV (100 %) [52]. Three-dimensional (3D) reconstructed images of multidetector CT are useful in differentiating LNs from accompanying vessels and detecting small nodes [54]; see Fig. 3.

Fig. 3
figure 3

Coronal reconstructed CT images have the advantage in discriminating pelvic lymph nodes from adjacent vessels. a Multiple metastatic lymph nodes (arrowheads) spreading along the common and external iliac arteries were clearly demonstrated on the coronal enhanced CT image. Additionally, a metastatic mass (hollow asterisk) with destruction of the iliac bone and pelvic mass (asterisk) above the bladder were noted. b Coronal precontrast CT image displayed an enlarged external iliac lymph node, which was confirmed as reactive hyperplasia

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MRI

In spite of the excellent soft tissue resolution, conventional MRI cannot provide higher diagnostic value than CT does since its main diagnostic standards still rely on the structural features of LNs [43]. The sensitivity, specificity, accuracy, PPV, and NPV of conventional MRI in the assessment of pelvic LNs for all tumor types are 58–95.8, 15.4–78.5, 41.9–97.8, 15.4–85.7, and 47.4–97.8 %, respectively [55–58]. The signal differences between positive and negative nodes on T1- and T2-weighted images are not significant [59]. Although extracapsular nodal spread and necrosis were more easily demonstrated on MRI than on CT and high specificities (94 and 100 % respectively) were reported in differentiating pelvic hyperplasia and malignant nodes, their sensitivities were extremely low (21 and 15 %) [60]; see Fig. 4. Even in gadolinium-enhanced MRI, a simple comparison of signal alternations before and after enhancement is not an obvious help in identifying the LN status [43, 61]. Fischbein et al. noted the enhancement kinetics of malignant and benign LNs were different. Malignant LNs demonstrated a significantly longer peak time, lower peak enhancement, lower maximum slope, and slower washout slope on the time/signal curves, which might indicate tumors have lower transfer of contrast agent to tissue and a decreased volume of extravascular and extracellular space compared to normal or reactive nodes. However, the results of the studies on enhancement kinetics are difficult to reproduce [62].

Fig. 4
figure 4

A 78-year-old female patient with anorectal cancer. a Axial enhanced CT showed bilateral enhanced obturator and internal iliac lymph nodes (arrows) with slightly hetrogeneous enhancement and ill-defined margins. b T1-weighted MR image clearly displayed necrosis (hollow arrow) within these metastatic nodes as well as extracapsular extension (dashed arrow)

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Functional Imaging

DWI

The imaging basis of DWI is to detect the diversity of microscopic water molecular diffusion movement in different tissues and consequently reflect their biophysical characteristics and changes [63]. This technology has been widely used in the evaluation of lymphopathy and shows a significantly higher sensitivity in detecting lymph nodes compared to conventional CT and MRI [58, 64], even to PET/CT [65]. The sensitivity, specificity, and accuracy of DWI are 57–86, 79–85.3, and 70-85.6 % for prostate cancer [64, 66], 83.3–87, 51.2–80, and 57.0–90.2 % for uterine cancer [67••, 68], and 80, 76.9, and 78.3 % for colorectal cancers [65], respectively. As the index of quantitative assessment of DWI, the apparent diffusion coefficient (ADC) value is commonly demonstrated at a significantly lower level in malignant LNs than in benign LNs [69]; see Fig. 5. The possible cause is that the water molecular movement is less restricted in benign nodes than in malignant ones because of their higher cellular density and less extracellular space [70]. In a study of cervical cancer, Lin et al. identified the relative ADC value was significantly lower in metastatic nodes than in non-metastatic nodes, 0.06 versus 0.21 × 10−3 mm2/s, p < 0.001 [58]. However, two inherent weaknesses limit the use of this modality in lymphopathy. First, its diagnostic accuracy is not very reliable in normal size nodes with micrometastasis because of image distortion and relatively poor spatial resolution [71]. Innovations of DWI-related technologies, such as parallel imaging, periodically rotated overlapping parallel lines, and short time inversion recovery DWI, may improve the detection sensitivity somehow [72, 73]. Second, a limitation of DWI is that there is a great deal of overlap of the ADC values between benign and malignant nodes. Hyperplasia and other benign pathological alternations (such as abscesses) also can restrict water diffusion within nodes, thus leading to similarly low ADC values as those of malignant nodes. Roy et al. pointed out that there was no significant difference in ADC values among the involved lymph nodes, control iliac nodes, and control inguinal nodes, with the mean ADC value ± standard deviation (×10−3 mm2/s) being 924 ± 217, 968 ± 182, and 1,036 ± 181, respectively [74].

Fig. 5
figure 5

A 88-year-old female patient with metastatic adenocarcinoma from unknown primary tumor. a Axial T2-weighted MR image revealed enlarged metastatic lymph nodes (arrows) in the left internal and external iliac chain (the largest one was 3 × 4.6 cm) as well as a subcentimeter reactive lymph node (hallow arrow) was detected in the right deep inguinal area. Also noted was a fibroid (asterisk) in the posterior wall of uterus. b Enlarged left iliac lymph nodes (arrows) manifested heterogeneous enhancement on enhanced T1-weighted MR image. c All bilateral pelvic lymph nodes displayed high signal while the fibroid did not show any abnormal signal on diffusion image with a b value of 600 mm2/s. d The ADC value of metastatic node (arrow) adjacent to left internal iliac vessels was lower than the value of benign node (hallow arrow) located in right inguinal area on ADC map, 0.75 versus 0.94 × 10−3 mm2/s

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USPIO

Lymphotropic MR contrast is another hopeful innovation in MR lymphography, with the most commonly used being USPIO (ferumoxtran-10). USPIO is a cell-specific contrast medium, which extravasates through the vascular wall to the interstitial space, then is transported to LNs via lymphatic vessels and internalized by macrophages. The normal parts of nodes with uptake of USPIO in macrophages show a signal drop on the T2*-weighted sequence due to the effect of iron oxide; on the contrary, the tumor deposit parts of nodes keep relatively high signals for lack of normal macrophages. This signal contrast forms the diagnostic basis of USPIO. So far, USPIO has been the most sensitive and specific non-invasive imaging modality in LN detection. Its sensitivity, specificity, accuracy, PPV, and NPV on a patient-by-patient basis reached 90, 80–100, 87–95.7, 67–97.5, and 93-100 %, respectively [75, 76••, 77]. With a high-resolution T2*-weighted sequence, this contrast may further improve the detection ability on micrometastatic deposits in normal-size nodes [78]; see Fig. 6. Harisinghani et al. reported relatively satisfying diagnostic results on nodes with a short-axis diameter less than 5 mm using ferumoxtran-10. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value on a node-by-node basis were 41.1, 98.1, 90.4, 77.7 and 91.3 %, respectively [76]. Unfortunately, without approval by the FDA, ferumoxtran-10 is still unavailable in clinics. Moreover, being time consuming in both examination and review is an underlying obstacle to gaining wide acceptance. Thoeny et al. reliably decreased the reading time of USPIO from 80 to 13 min utilizing a combined approach called USPIO–DW-MRI in patients with prostate cancer [75].

Fig. 6
figure 6

Lymphotropic nanoparticle enhanced MRI (Ferumoxtran-10) allows for characterization of small size (diameter <10 mm) lymph nodes in pelvis. a Precontrast T2* image showed there were two small benign external iliac lymph nodes (arrows), with a big hilar (asterisk) in the larger one. b Both nodes showed homogeneous decrease of the signal. c Another round shape lymph node presented slightly high signal on precontrast T2* image. d The signal of a involved part of the node (asterisk) decreased on postcontrast image, while the uninvolved part (hallow asterisk) kept the sightly high signal

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PET/CT (MRI)

PET is a functional nuclear imaging method for detecting pairs of gamma rays emitted indirectly by special radioactive tracers. [18F]-fluoro-2-deoxy-d-glucose (18F-FDG) is the most popular tracer at present, which can reflect the increased glucose metabolism in most types of malignant tumor cells. However, its application in prostate cancer does not proceed smoothly for three reasons: one is that most prostate cancers are not very 18F-FDG avid; second is the overlap of FDG uptake noted among normal, hyperplastic, and malignant tissues, especially when lesions are small or diffuse or mixed with noncancerous cells; third, the excretion of FDG through the bladder can be confused with the spread in prostate cancer [79]. As an alternative to 18F-FDG, [11C]-choline shows good outcomes in staging prostate cancer on PET. The increase in cell proliferation and CHKα expression in prostate cancer cells induces increased uptake of choline and its by-products [80], consequently showing a signal increase on PET. Fusion PET with CT or MRI is helpful in improving the spatial resolution and consequently strengthening the detection ability on nodes with diameters less than 1 cm or located adjacent to the primary tumor [81]. In ovarian cancer, the accuracy, sensitivity, specificity, PPV, and NPV of PET/CT could reach 83.3, 98.2, 95.6, 90.9, and 96.5 %, respectively [82]; in cervical cancer, the corresponding values were 99.3, 72, 99.7, 81, and 99.5 %, respectively [83••]; in prostate cancer, the corresponding values of 11C-choline PET/CT were 60.0, 97.6, 87.7, 90.0, and 87.2 %, respectively [84]. In addition, the overlapping uptake between malignant and benign nodes also makes the interpretation more challenging; see Fig. 7. Familiarity with the nodal drainage pathways may help to make a more appropriate judgment. For instance, abnormal uptake in the mid-external iliac chains and more proximally should lead to high suspicion of metastasis in prostate cancer. In contrast, low-level 11C-choline nodal activity is frequently seen in benign inguinal LNs [85•].

Fig. 7
figure 7

A 62-year-old female patient with pelvic metastases from cervical cancer. a Axial enhanced CT image demonstrated a 3.4 × 4.0 cm metastatic lymph node (arrow) adjacent to right external iliac vessels, with moderate homogeneous enhancement. b The enlarged external iliac lymph node (arrow) showed significant high 18-FDG uptake on PET image. c Another right inguinal lymph node (arrow) with a short diameter of 9 mm was noted on the lower axial CT image in the same patient. d This inguinal lymph node (arrow) also showed moderate FDG uptake on PET image but was confirmed as reactive node

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SPECT/CT (MRI) LSG

SPECT/CT (MRI) LSG is another hybrid nuclear method combining conventional LSG with 3D CT or MRI images. The most common radiotracer is 99mTc nanocolloid. This modality is usually adopted in preoperative SLN mapping owing to its better anatomic location [86]. SPECT/CT LSG presented a significantly higher detection rate of a singular SLN than of planar LSG, 92.2 versus 84.3 % in cervical cancer [87] and 98 versus 91 % in prostate cancer [88], especially when SLNs are located near the injection area, such as the parametrial area in cervical cancer.

ICT (MRI) LG

ICT (MRI) LG is a newly emerging technology on LN mapping and currently has only been used in preclinical and limited clinical trials. In this modality, small-sized particulate contrast agents, subcutaneously injected, travel into the lymphatic vessels because of the increased permeability of the fenestrated endothelial lining of the distal lymphatic capillaries and then accumulate in the afferent LNs [89]. Common contrast agents include iopamidol in CT and gadoterate meglumine, gadodiamide, gadofluoramide, and gadofluorine 8 in MRI. The peritumoral area is commonly chosen as the injection site, and the optimal scan time is about 30 min to 2 h after injection. These technologies provide the visualization of the direct connection between the primary SLN and its afferent lymphatic vessels as well as high-resolution anatomic images of lymphatic basin [90, 91•]. In a study of cervical cancer, IMRLG demonstrated a significantly higher accuracy in the detection of SLN than blue dye lymphography, 85 versus 61 %, with an accuracy, sensitivity, specificity, PPD, and NPD of 92.9, 80, 95.7, 100, and 95.7 %, respectively. However, this techology is not suitable for use in pelvic LNs because it is difficult to find a proper injection site for deep pelvic tumors [90]. Besides, the large volume of contrast agent administered subcutaneously may be an obstacle to its application [91].

New Modalities

Besides these routine imaging methods discussed above, some new emerging technologies, such as photoacoustic imaging and targeting nanotechnology, have contributed to detecting lymphatic metastasis. Photoacoustic imaging is a hybrid biomedical imaging modality based on the photoacoustic effect. In this technology, non-ionizing laser pulses are delivered into biological tissues. Some of the delivered energy leads to transient thermoelastic expansion and a pressure wave (i.e., photoacoustic signal) that can be detected by ultrasound [92••]. The signal is proportional to the local energy deposition and reveals physiologically specific optical absorption contrast, based on which 2D or 3D images of the targeted areas can be formed. The tracers used in photoacoustic imaging for SLN mapping include indocyanine green, methylene blue, near-infrared dye, and gold nanoparticles. Song et al. demonstrated that a new class of lymph node tracers, Au nanocages (near-infrared gold nanocages), allows identifying SLNs as deep as 33 mm below the skin surface with good contrast, and these tracers can be easily bioconjugated with antibodies for targeting specific receptors [93]. Although this modality has shown good potential in noninvasive imaging for SLNs in breast cancer and melanoma patients, new contrast agents with higher penetrability and sensitivity need to be developed if extended to deeper abdominal and pelvic regions. Targeting nanotechnology is another potential modality in lymph node mapping with conjugation of biorecognition polymers to nanoparticles, which also shows good prospects in tumor therapy. Hyaluronan, quantum dots, and iron oxide nanoparticles are common nanoconjugates. Depending on the nanoconjugate of hyaluronan with a fluorescent tag, Cai et al. clearly localized nodes with hyaluronan surrounding an implanted breast tumor and also decreased breast cancer progression by a hyaluronan-doxorubicin nanoconjugate in vivo mouse study [94].

Conclusion

In this review, we summarized the general and specific pelvic LN drainage pathways as well as SLN landing sites in each individual pelvic tumor. Moreover, the basic principles and characteristics of conventional and emerging imaging modalities for the assessment of pelvic LNs are also elaborated in this article. Combining the lymphatic drainage and imaging information will help radiologists and surgeons make better decisions about the diagnosis and treatments in pelvic diseases. Moreover, the technical advances in functional MRI, lymphotropic MR contrast, hybrid nuclear methods, and other new imaging modalities might eliminate the limitations to the detection of micrometastases within normal-size LNs in the future.