European Journal of Radiology 34 (2000) 257 – 264 Iron oxide-enhanced MR lymphography: initial experience Marie-France Bellin *, Catherine Beigelman, Sophie Precetti-Morel Department of Radiology, Ho ˆpital Pitie ´ -Salpe ˆtie `re, 83 Bouleard de l’Ho ˆpital, 75651 Paris Cedex 13, France Received 11 January 2000; accepted 10 March 2000 Abstract The detection of nodal metastases is of utmost importance in oncologic imaging. Ultrasmall superparamagnetic iron oxide particles (USPIO) are novel contrast agents specifically developed for MR lymphography. After intravenous administration, they are taken up by the macrophages of the lymph nodes, where they accumulate. They reduce the signal intensity (SI) of normally functioning nodes on postcontrast T2-and T2*-weighted images through the magnetic susceptibility effects on iron oxide. Metastatic nodes, in which macrophages are replaced by tumor cells, show no significant change in SI on postcontrast T2-and T2*-weighted images. Early clinical experience suggests that USPIO-enhanced MR lymphography improves the sensitivity and specificity for the detection of nodal metastases. It also suggests that micrometastases could be detected in normal-sized nodes. This article reviews the physiochemical properties of USPIO contrast agents, their enhancement patterns, and early clinical experience. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Lymphatic system, MR; Lymphatic system; Neoplasms; Magnetic resonance (MR); Contrast enhancement www.elsevier.nl/locate/ejrad 1. Introduction Ultrasmall superparamagnetic iron oxide particles (USPIO) are novel magnetic resonance (MR) contrast agents specifically developed for intravenous MR lymphography [1–7]. They are specific for the reticulo– endothelial-system (RES) and provide information on lymph node morphology and function. They have been used to improve the detection of node metastases, and are still in the experimental stage. Local-regional lymph node involvement is a key prognostic factor and an important determinant of cancer treatment choices. In particular, it is an impor- tant element in choosing the most appropriate treat- ment modality, planning surgical or radiation treatment, and monitoring the response to therapy. After physical examination, computed tomography (CT) is currently the most frequently used method for assessing lymph node status in cancer staging. Magnetic resonance imaging (MRI) can also be used for this purpose but generally has lower spatial resolution, while ultrasonography (US) provides less contrast. The only CT and MR imaging criterion that is generally accepted in the evaluation of node metastases is the size of the node. However, false-negative findings for nor- mal-size metastatic nodes limit staging capabilities. An- other limitation is that US, CT and unenhanced MRI cannot distinguish metastatic nodes from non metastatic reactive nodes. Borderline-sized nodes re- main indeterminate in these techniques. Conventional lymphography has virtually been abandoned, as it in- volves a lengthy delivery technique and its usefulness is limited to pelvic and lumbar nodal chains. Surgical lymph node dissection is efficient but invasive; pub- lished data on the accuracy of histologic analysis of intraoperative frozen section of nodes conflict, and rates of false-negative results as high as 33% have been reported in pelvic node analyses [8]. The disadvantages of size discrimination with current cross-sectional imag- ing techniques, together with the morbidity and length of surgical procedures, have prompted extensive re- search aimed at developing tissue-specific imaging methods, including USPIO-enhanced MR lymphogra- phy. This article reviews the development of superpara- magnetic iron oxide compounds, together with their physicochemical features, imaging characteristics, and initial clinical experience. * Corresponding author. Tel.: +33-1-42176321; fax: +33-1- 42176338. E-mail address: marie-france.bellin@psl.ap-hop-paris.fr (M.-F. Bellin). 0720-048X/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0720-048X(00)00204-7