Contrast-enhanced MR imaging of lymph nodes in cancer patients

Abstract

The accurate identification and characterization of lymph nodes by modern imaging modalities has important therapeutic and prognostic significance for patients with newly diagnosed cancers. The presence of nodal metastases limits the therapeutic options, and it generally indicates a worse prognosis for the patients with nodal metastases. Yet anatomic imaging (CT and MR imaging) is of limited value for depicting small metastatic deposits in normal-sized nodes, and nodal size is a poor criterion when there is no extracapsular extension or focal nodal necrosis to rely on for diagnosing nodal metastases. Thus, there is a need for functional methods that can be reliably used to identify small metastases. Contrast-enhanced MR imaging of lymph nodes is a non-invasive method for the analysis of the lymphatic system after the interstitial or intravenous administration of contrast media. Moreover, some lymphotrophic contrast media have been developed and used for detecting lymph node metastases, and this detection is independent of the nodal size. This article will review the basic principles, the imaging protocols, the interpretation and the accuracies of contrast-enhanced MR imaging of lymph nodes in patients with malignancies, and we also focus on the recent issues cited in the literature. In addition, we discuss the results of several pre-clinical studies and animal studies that were conducted in our institution.

Keywords: Contrast media; Lymph node metastasis; Magnetic resonance (MR); Magnetic resonance (MR) lymphography.

Fig. 1

Uptake mechanism of ferumoxtran-10. A. Intravenously injected particles slowly extravasate from vascular space to interstitial space. B. Particles are then transported to lymph nodes via lymphatic vessels. C. In lymph nodes, particles are internalized by macrophages. D. These intracellular iron-containing particles cause normal nodal tissue to have low signal intensity. Disturbances of lymph flow or nodal architecture by metastases lead to abnormal accumulation patterns, as is depicted by lack of decreased signal intensity.

Fig. 2

Patterns of ultrasmall superparamagnetic iron oxide (USPIO) uptake in benign and malignant lymph nodes on contrast-enhanced MRI of Lymph nodes, and respective interpretations of these patterns.

Fig. 3

Benign and metastatic lymph nodes on ultrasmall superparamagnetic iron oxide (MION [monocrystalline iron oxide nanoparticle]-47)-enhanced MR imaging in three rabbit VX2 tumor models. A. T2^*-weighted MR image obtained 24 hours after intravenous administration of MION-47 (2.6 mg of iron per kilogram of body weight) shows homogeneous dark signal intensity of benign left paraaortic lymph node (arrow). B. T2^*-weighted MR image obtained 24 hours after intravenous administration of MION-47 (2.6 mg of iron per kilogram of body weight) shows focal high signal intensity region (arrowhead) in right paraaortic lymph node (arrow), which was proven to be metastatic focus by histopathology. C. T2^*-weighted MR image obtained 24 hours after intravenous administration of MION-47 (2.6 mg of iron per kilogram of body weight) shows malignant right paraaortic lymph node (arrow), which was totally replaced with metastatic tissue.

Fig. 4

Coronal T1-weighted spin-echo MR image, T2^*-weighted gradient-echo MR images, CT image, PET image, integrated PET/CT image and photomicrograph of right iliac lymph node of rabbit four weeks after VX2 tumor inoculation, and images were taken with rabbit in prone position. A. T1-weighted spin echo image (400/12) obtained before injection of ultrasmall superparamagnetic iron oxide shows right iliac lymph node (arrow) with low signal intensity. B. T2^*-weighted gradient-echo image (400/24, flip angle of 20°) obtained before injection of ultrasmall superparamagnetic iron oxide shows right iliac lymph node (arrow) with high signal intensity in upper portion and intermediate signal intensity in lower portion. C. T2^*-weighted gradient-echo image (400/24, flip angle of 20°) obtained 24 hours after injection of ultrasmall superparamagnetic iron oxide shows functional tissue of right iliac lymph node with uniform low signal intensity in upper portion, and small amount of malignant tissue (arrow) with high signal intensity in lower portion. D-F. PET and integrated PET/CT images show right iliac lymph node (arrows) without increased fluorodeoxyglucose uptake. G. Photomicrograph of histopathologic specimen shows right iliac lymph node with 3.2 mm malignant tissue focus (arrows) (Hematoxylin & Eosin stain; ×5).

Fig. 5

Oblique coronal maximum intensity projection image from T1-weighted 3D gradient-echo MRI sequence obtained 60 minutes after interstitial administration of 5 µmol/kg gadofluorine M in VX2 tumor rabbit model. Metastases in right popliteal (arrowhead) and iliac (thick arrow) lymph nodes are demonstrated as filling defects. Lymphatic vessels (thin arrow) are also sharply delineated.

Fig. 6

Coronal T1-weighted spin-echo MR images, T2^*-weighted gradient-echo MR images and photomicrograph of left parotid lymph node of rabbit four weeks after VX2 tumor inoculation (Choi et al. [40], reprint with permission from Radiology). A. T1-weighted spin echo image (400/12) obtained before injection of gadofluorine M shows left parotid lymph node (arrowheads) with low signal intensity, and VX2 tumor (curved arrow) with slightly high signal intensity. B. T1-weighted spin-echo image (400/12) obtained 30 minutes after injection of gadofluorine M (0.05 mmol gadolinium per kilogram body weight) shows strong enhancement of functional tissue (arrowheads) of left parotid lymph node and malignant tissue (arrow) shows slight enhancement. High contrast between enhanced functional lymph node tissue and only slightly enhanced malignant tissue enables more obvious detection of metastasis than in (D). VX2 tumor (curved arrow) with peripheral rim enhancement is also noted. C. T2^*-weighted gradient-echo image (400/24, flip angle of 20°) obtained before injection of MION-47 shows left parotid lymph node (arrowheads) with high signal intensity, and VX2 tumor (curved arrow) with high signal intensity. D. T2^*-weighted gradient-echo image (400/24, flip angle of 20°) obtained 24 hours after injection of MION-47 (2.6 mg of iron per kilogram of body weight) shows functional tissue (arrowheads) of left parotid lymph node with uniform low signal intensity and peripheral malignant tissue (arrow) with high signal intensity, which shows poor contrast between malignant tissue and surrounding parenchymal tissue. High signal intense VX2 tumor (curved arrow) with peripheral low signal intensity is also noted. E. Photomicrograph of histopathologic specimen shows malignant tissue (arrows) with maximum diameter of 2 mm in subcapsular portion of left parotid lymph node (Hematoxylin & Eosin stain; original magnification, ×5).