Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for lymph nodes. Relaxation time measurements and magnetic resonance (MR) imaging were performed in rats with normal lymph nodes and in rats with lymph node metastases. In normal animals, lymph node relaxation times decreased maximally within 24-48 hours after intravenous administration of USPIO. Twenty-four hours after administration, the T2 of normal lymph nodes had decreased from 74 msec +/- 2.2 to 30 msec +/- 0.7 (USPIO, 40 mumol of iron per kilogram) or 15 msec +/- 0.0 (200 mumol Fe/kg), whereas the T2 of metastatic nodes did not change. MR imaging of the animal model of nodal metastases confirmed the hypothesis that intravenously administered USPIO decreases signal intensity of normal but not metastatic nodes. A single intravenous administration of USPIO may allow detection of nodal metastases on the basis of signal intensity characteristics rather than the currently used, insensitive size characteristics.     

Contrast-Enhanced MR Imaging of Lymph Nodes in Cancer Patients

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.     

Experimental lymph node metastases: enhanced detection with MR lymphography

Magnetic resonance (MR) lymphography with superparamagnetic iron oxide (AMI-25) as a contrast agent was developed in an animal model with tumor-bearing lymph nodes. After interstitial administration of 20 mumol of iron per kilogram of body weight into the footpads of rats, the T2 of popliteal and paraaortic lymph nodes decreased from 67 msec +/- 8.2 to 9.5 msec +/- 0.9 and 9.3 msec +/- 0.9, respectively. T2 relaxation times of lymph nodes containing metastases showed a significantly higher value (61 msec +/- 6.2, P less than .005) after interstitial administration of the contrast agent. Intravenous administration of AMI-25 did not produce enhancement of normal or metastatic lymph node relaxation times. The signal intensity of normal lymph nodes decreased profoundly on spin-echo MR images (repetition time of 500 msec, echo time of 30 msec) after interstitial administration, whereas lymph nodes with metastases showed no significant change in signal intensity. Experimental results indicate that MR lymphography may potentially increase the sensitivity of MR imaging the detection of lymphatic malignancy.     

Role of diffusion-weighted MR imaging in cervical lymphadenopathy

The role of diffusion-weighted magnetic resonance imaging (MRI) for differentiation between various causes of cervical lymphadenopathy was evaluated. In a prospective study, 31 untreated patients (22 males and nine females, aged 5–70 years) with 87 cervical lymph nodes underwent diffusion-weighted MRI before performance of neck dissection (n=14), surgical biopsy (n=9) or core biopsy (n=8). Diffusion-weighted MR images were acquired with a b factor of 0 and 1,000 s/mm² using single-shot echo-planar sequence. Apparent diffusion coefficient (ADC) maps were reconstructed for all patients. The signal intensity of the lymph nodes was assessed on images obtained at b=0 or 1,000 s/mm² and from the ADC maps. The ADC value of lymph nodes was also calculated. On the ADC map, malignant nodes showed either low (n=52) or mixed (n=20) signal intensity and benign nodes revealed high (n=13) or low (n=2) signal intensity. The mean ADC value of metastatic (1.09±0.11×10⁻³ mm²/s) and lymphomatous (0.97±0.27×10⁻³ mm²/s) lymph nodes was significantly lower than that of benign (1.64±0.16×10⁻³ mm²/s) cervical lymph nodes (P<0.04). When an ADC value of 1.38×10⁻³ mm²/s was used as a threshold value for differentiating malignant from benign lymph nodes, the best results were obtained with an accuracy of 96%, sensitivity of 98%, specificity of 88%, positive predictive value of 98.5% and negative predictive value of 83.7%. The smallest detected lymph node was 0.9 cm. In conclusion, diffusion-weighted MRI with ADC mapping is a new promising technique that can differentiate malignant from benign lymph nodes and delineate the solid viable part of the lymph node for biopsy. This technique provides additional useful physiological and functional information regarding characterization of cervical lymph nodes.     

Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathologic comparison

PURPOSE: To evaluate signal intensity and border characteristics of lymph nodes at high-spatial-resolution magnetic resonance (MR) imaging in patients with rectal cancer and to compare these findings with size in prediction of nodal status. MATERIALS AND METHODS: Forty-two patients who underwent total mesorectal excision of the rectum to determine if they had rectal carcinoma were studied with preoperative thin-section MR imaging. Lymph nodes were harvested from 42 transversely sectioned surgical specimens. The slice of each lymph node was carefully matched with its location on the corresponding MR images. Nodal size, border contour, and signal intensity on MR images were characterized and related to histologic involvement with metastases. Differences in sensitivity and specificity with border or signal intensity were calculated with CIs by using method 10 of Newcombe. RESULTS: Of the 437 nodes harvested, 102 were too small (<3 mm) to be depicted on MR images, and only two of these contained metastases. In 15 (68%) of 22 patients with nodal metastases, the size of normal or reactive nodes was equal to or greater than that of positive nodes in the same specimen. Fifty-one nodes were above the area imaged, and seven of these contained metastases. The diameter of benign and malignant nodes was similar; therefore, size was a poor predictor of nodal status. If a node was defined as suspicious because of an irregular border or mixed signal intensity, a superior accuracy was obtained and resulted in a sensitivity of 51 (85%) of 60 (95% CI: 74%, 92%) and a specificity of 216 (97%) of 221 (95% CI: 95%, 99%). CONCLUSION: Prediction of nodal involvement in rectal cancer with MR imaging is improved by using the border contour and signal intensity characteristics of lymph nodes instead of size criteria.     

Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging

PURPOSE: To prospectively evaluate ferumoxtran-10-enhanced magnetic resonance (MR) imaging for nodal staging in patients with urinary bladder cancer. MATERIALS AND METHODS: Fifty-eight patients with proved bladder cancer were enrolled. Results of MR imaging performed before and after injection of ferumoxtran-10 were compared with histopathologic results in surgically removed lymph nodes. High-spatial-resolution three-dimensional T1-weighted magnetization-prepared rapid acquisition gradient-echo (voxel size, 1.4 x 1.4 x 1.4 mm) and T2*-weighted gradient-echo (voxel size, 0.8 x 0.8 x 3.0 mm) sequences were performed before and 24 hours after injection of ferumoxtran-10 (2.6 mg iron per kilogram of body weight). On precontrast images, lymph nodes were defined as malignant by using size and shape criteria (round node, >8 mm; oval, >10 mm axial diameter). On postcontrast images, nodes were considered benign if there was homogeneous decrease in signal intensity and malignant if decrease was absent or heterogeneous. Qualitative evaluation was performed on a node-to-node basis. Sensitivity, specificity, predictive values, and accuracy were evaluated with logistic regression analysis. RESULTS: In 58 patients, 172 nodes imaged with use of ferumoxtran-10 were matched and correlated with results of node dissection. Of these, 122 were benign and 50 were malignant. With nodal size and shape criteria, accuracy, sensitivity, specificity, and positive and negative predictive values on precontrast images were 92%, 76%, 99%, 97%, and 91%, respectively; corresponding values on postcontrast images were 95%, 96%, 95%, 89%, and 98%. In the depiction of pelvic metastases, sensitivity and negative predictive value improved significantly at postcontrast compared with those at precontrast imaging, from 76% to 96% (P < .001) and from 91% to 98% (P < .01), respectively. At postcontrast imaging, metastases (4-9 mm) were prospectively found in 10 of 12 normal-sized nodes (<10 mm); these metastases were not detected on precontrast images. Postcontrast images also showed lymph nodes that were missed at pelvic node dissection in two patients. CONCLUSION: Ferumoxtran-10-enhanced MR imaging significantly improves nodal staging in patients with bladder cancer by depicting metastases even in normal-sized lymph nodes.     

Early MR lymphography with gadofluorine M in rabbits

PURPOSE: To investigate the dose and time dependency of gadofluorine M for lymph node imaging and the detection of lymph node metastases in an animal model and to compare gadofluorine M with Gadomer (both, Schering, Berlin, Germany) for lymph node enhancement. MATERIALS AND METHODS: Enhancement of popliteal and iliac lymph nodes was studied in VX2 tumor-bearing rabbits before injection and at 5-120 minutes and 24 hours after intravenous bolus injection of 0.025, 0.05, and 0.1 mmol gadolinium per kilogram of body weight gadofluorine M (six rabbits) or 0.5 mmol/kg Gadomer (eight rabbits). Effects of treatment and time point at enhancement were evaluated with repeated measures analysis of variance. Means were separated with all-pairs comparison with Tukey-Kramer adjustment. After 1.5-T magnetic resonance (MR) imaging, lymph nodes were removed, and prepared sections were stained with hematoxylin-eosin for microscopic examination. RESULTS: MR images in VX2 tumor-bearing rabbits revealed rapid and strong signal intensity increase in the functional lymph node tissue by 15 minutes after intravenous injection of gadofluorine M. Maximum enhancement of 165%-309% was observed 60-90 minutes after injection (enhancement with 0.05 and 0.1 mmol/kg significantly different from that with 0.025 mmol/kg, P < or =.05). Metastatic tissue showed only slight enhancement at early time points, resulting in high-contrast differentiation between functional and metastatic tissue. Intravenous injection of the blood-pool agent Gadomer induced only short and inhomogeneous lymph node enhancement (enhancement significantly lower [P < or =.05] than that with gadofluorine M). CONCLUSION: Findings in the study showed that gadofluorine M produces rapid lymph node accumulation. Diagnosis of lymph node metastases was shown with intravenous injection of gadofluorine M with a minimum effective diagnostic dose of 0.025 mmol/kg.     

Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma.

The purpose of this study was to evaluate the clinical efficacy of ultrasmall superparamagnetic iron oxide particles as a magnetic resonance (MR) contrast agent in differentiating metastatic from benign lymph nodes. Eighteen patients with primary lung malignancy and suspected regional lymph node metastases underwent MR imaging before and after Combidex(R) infusion in a multi-institutional study. All MR sequences were interpreted by one or more board-certified radiologists experienced in imaging thoracic malignancy. Each patient was evaluated for the number and location of lymph nodes, homogeneity of nodal signal, and possible change of MR signal post contrast. All patients underwent resection or sampling of the MR-identified lymph node(s) 1-35 day(s) post contrast MR imaging. In all, 27 lymph nodes or nodal groups were available for histopathologic correlation. Combidex had a sensitivity of 92% and a specificity of 80% in identifying pathologically confirmed metastatic mediastinal lymph nodes. Based on our preliminary data, Combidex MR imaging may provide additional functional information useful in the staging of mediastinal lymph nodes.     

Axillary lymph node metastases in patients with breast carcinomas: assessment with nonenhanced versus uspio-enhanced MR imaging

PURPOSE: To prospectively assess the accuracy of nonenhanced versus ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging for depiction of axillary lymph node metastases in patients with breast carcinoma, with histopathologic findings as reference standard. MATERIALS AND METHODS: The study was approved by the university ethics committee; written informed consent was obtained. Twenty-two women (mean age, 60 years; range, 40-79 years) with breast carcinomas underwent nonenhanced and USPIO-enhanced (2.6 mg of iron per kilogram of body weight intravenously administered) transverse T1-weighted and transverse and sagittal T2-weighted and T2*-weighted MR imaging in adducted and elevated arm positions. Two experienced radiologists, blinded to the histopathologic findings, analyzed images of axillary lymph nodes with regard to size, morphologic features, and USPIO uptake. A third independent radiologist served as a tiebreaker if consensus between two readers could not be reached. Visual and quantitative analyses of MR images were performed. Sensitivity, specificity, and accuracy values were calculated. To assess the effect of USPIO after administration, signal-to-noise ratio (SNR) changes were statistically analyzed with repeated-measurements analysis of variance (mixed model) for MR sequences. RESULTS: At nonenhanced MR imaging, of 133 lymph nodes, six were rated as true-positive, 99 as true-negative, 23 as false-positive, and five as false-negative. At USPIO-enhanced MR imaging, 11 lymph nodes were rated as true-positive, 120 as true-negative, two as false-positive, and none as false-negative. In two metastatic lymph nodes in two patients with more than one metastatic lymph node, a consensus was not reached. USPIO-enhanced MR imaging revealed a node-by-node sensitivity, specificity, and accuracy of 100%, 98%, and 98%, respectively. At USPIO-enhanced MR imaging, no metastatic lymph nodes were missed on a patient-by-patient basis. Significant interactions indicating differences in the decrease of SNR values for metastatic and nonmetastatic lymph nodes were found for all sequences (P < .001 to P = .022). CONCLUSION: USPIO-enhanced MR imaging appears valuable for assessment of axillary lymph node metastases in patients with breast carcinomas and is superior to nonenhanced MR imaging.     

MR contrast agents in lymph node imaging

The detection of tumor metastases in lymph nodes is clinically important for tumor staging and therapy planning in cancer patients. However, differentiating between malignant and benign lymph nodes is still a problem because current imaging modalities rely only on the size and shape of the lymph nodes. Thus, small metastases in normal-sized lymph nodes can be missed, and it is difficult to differentiate enlarged nodes (benign hyperplasia versus malignant disease). Therefore, a specific lymphotropic contrast agent is needed to obtain a high contrast between functional and metastatic tissue. Contrast-enhanced MR lymphography is a noninvasive method for the analysis of the lymphatic system after interstitial (intracutaneous or subcutaneous) or intravenous application of contrast media. Interstitial MR lymphography using extracellular, liposomal, polymeric, lipophilic or particulate contrast agents results in high accumulation in regional lymph nodes. The systemic administration of a lymphotropic contrast medium is needed to address each individual lymph node. Ultrasmall superparamagnetic iron oxide particles are in late-stage clinical development for this indication, but they take 24h to show sufficient contrast. Recently, a gadolinium-type contrast agent (Gadofluorine M) was described that detected lymph node metastases within 60 min of intravenous injection.     

Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis.

PURPOSEThe purpose of this study was to ascertain the usefulness of MR imaging in the diagnosis of nodal metastasis of papillary thyroid carcinoma and to establish the most indicative MR criteria of metastasis.METHODSPathologic records and MR images in 50 patients with papillary thyroid carcinoma were reviewed. Each neck was divided into four nodal levels, so that 200 nodal levels were assessed in all. The maximum of the minimum transverse diameters of the lymph nodes on each nodal level measured on MR images and the certainty of metastasis as determined by a head and neck radiologist on the basis of morphologic aspects were compared with the pathologic findings by using receiver operating characteristic curves. The presence or absence of cystic nodes on each nodal level was also evaluated.RESULTSMetastasis was found on 87 (44%) of the nodal levels in 34 (68%) of the patients. A cystic node was identified on 33 (17%) of the nodal levels in 13 (26%) of the patients and was seen only on positive nodal levels. Morphologic diagnosis by the radiologist was better than that obtained by measurement. With the combined criteria of a cystic node or a node of 13 mm or more for the maximum of the minimum transverse diameters, specificity was 100% with an 82% accuracy and always indicated metastasis (100% positive predictive value). However, 41% of the metastatic nodes were missed with this criterion (59% sensitivity).CONCLUSIONMR imaging was useful for diagnosing metastatic nodes; a nodal diameter threshold of 13 mm or the presence of a cystic node strongly indicated metastasis from papillary thyroid carcinoma.     

Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study

PURPOSE: To determine the safety and efficacy of ferumoxtran 10-enhanced magnetic resonance (MR) imaging for diagnosis of metastases to lymph nodes and the clinical usefulness of ferumoxtran 10 in nodal staging. MATERIALS AND METHODS: One hundred fifty-two patients were injected with ferumoxtran 10. Readers independently evaluated precontrast MR images by using node size criteria and subjective assessment of other imaging features. Ferumoxtran 10-enhanced MR images were evaluated alone and paired with precontrast images for comparison. The diagnostic performances of precontrast MR size criteria and postcontrast MR imaging were evaluated with receiver operating characteristic (ROC) analysis. Lymph node signal intensity was correlated with histopathologic findings. MR imaging and histopathologic nodal stages were compared. RESULTS: Node-level sensitivity, specificity, and accuracy of precontrast MR imaging were 54%, 82%, and 68%, respectively, with node size criterion alone; 91%, 51%, and 71%, respectively, with subjective reader assessment; 85%, 85%, and 85%, respectively, with postcontrast MR imaging alone; and 83%, 77%, and 80%, respectively, with paired pre- and postcontrast MR imaging. Compared with size criteria, subjective reader assessment had higher sensitivity but substantially lower specificity. Areas under the ROC curve for pre- and postcontrast MR imaging were 0.76 and 0.83, respectively. Nonmetastatic nodes had significantly lower signal intensity than metastatic nodes on postcontrast T2-weighted MR images (P <.001). Postcontrast nodal staging was significantly more accurate than precontrast nodal staging (P <.01). Headache, back pain, vasodilatation, and urticaria each occurred in 6% of patients. CONCLUSION: Ferumoxtran 10-enhanced MR imaging was safe and effective and facilitated improved diagnostic performance. Use of iron oxide-enhanced MR imaging increased the positive predictive value by 20% and the accuracy by 14% compared with reader assessment. Differentiating patients with no nodal metastatic involvement was more reliable with ferumoxtran 10-enhanced MR imaging than with precontrast MR imaging.     

Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography.

OBJECTIVE: Accurate assessment of lymph node status before treatment is critical in the treatment of gynecologic cancers because the 5-year survival and treatment of women is influenced by lymph node involvement. The aims of this study were to investigate the ability of X-ray CT, MR imaging, and (18)F-FDG positron emission tomography (PET) to detect pelvic lymph node metastases by comparing imaging with histopathologic findings after lymph node dissection. MATERIALS AND METHODS: Eighteen patients with gynecologic cancers were studied by all three imaging methods before surgery. The images were initially reviewed with routine diagnostic conditions and then, subsequently, by two observers who were unaware of the clinical and histopathologic findings of the patients. The nodal sites were split into upper (aortic to common iliac bifurcations) and lower (common iliac bifurcations to inguinal ligament) iliac chains. All observers' results were statistically analyzed with specificity, sensitivity, positive and negative predictive values, Fisher's exact test (individual observers) or chi-square test (combined observers), and Cohen's kappa test. RESULTS: Eight of 18 patients had lymph node metastases at histology. Findings of all three modalities agreed in full in only one patient. CT correctly revealed 10 node-negative patients, whereas MR imaging was correct in eight of these patients. (18)F-FDG PET correctly depicted one patient with lymph nodes negative for tumor. CT was the most specific imaging modality (97.0%), with MR imaging and PET rendering values of 90.7% and 77.3%, respectively, but sensitivity of all modalities was low (CT, 48.1%; MR imaging, 53.7%; PET, 24.5%). Observer agreement for each modality was good; kappa values among all observers were 0.88 for CT, 0.85 for MR imaging, and 0.72 for PET. CONCLUSION: CT is the most specific modality for detecting lymph nodes positive for tumor in gynecologic cancers, whereas MR imaging is the most sensitive. The poor results of PET in the pelvis are attributed to urinary (18)F-FDG in the ureters or bladder, which may mask or imitate lymph node metastases.     

Assessment of metastatic cervical adenopathy using dynamic contrast-enhanced MR imaging

BACKGROUND AND PURPOSE: Morphologic assessment by conventional imaging methods of lymph node metastases in patients with squamous cell carcinoma of the head and neck is, at best, insensitive. Doppler sonography has shown that lymph node metastases exhibit alterations in the number of vessels and blood flow. We assessed the ability of dynamic contrast-enhanced MR imaging to differentiate normal from diseased nodes in this patient population. METHODS: Twenty-one patients with newly diagnosed squamous cell carcinoma and no previous treatment were studied with the use of a head and neck phased array surface coil. Anatomic imaging included high resolution T1-weighted, fat-saturated fast spin-echo T2-weighted, and contrast-enhanced T1-weighted imaging (0.99-1.32 mm(3) voxels). The dynamic contrast-enhanced MR imaging was performed by using a 2D fast spoiled gradient recalled sequence with single dose bolus injection of contrast agent. Calculated values included time to peak, peak enhancement, maximum slope, and washout slope for the enhancement. All patients underwent neck dissection as part of their indicated treatment, and imaging results were correlated with pathologic findings. RESULTS: Dynamic contrast-enhanced MR imaging and pathology comparisons were obtained for 68 nodes. There was significantly longer time to peak (P <.001), lower peak enhancement (P <.05), lower maximum slope (P <.01), and slower washout slope (P <.05) in the tumor-involved nodes compared with the normal nodes. CONCLUSION: Analysis of dynamic contrast-enhanced MR imaging can differentiate normal from diseased lymph nodes in patients with squamous cell carcinoma of the head and neck.     

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

Purpose

To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma.

Material & Methods

Fifty-two patients with malignant melanoma (female: n =?30, male: n =?22, mean age 50.5?±?16.0 years, mean tumor thickness 2.28?±?1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard.

Results

Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased.

Conclusion

In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

     

Dextran-coated superparamagnetic iron oxide,an MR contrast agent for assessing lymph nodes in the head and neck.

PURPOSETo investigate dextran-coated superparamagnetic iron oxide particles (BMS 180549) as an MR contrast agent for assessing lymph nodes.METHODSFive different doses ranging from 0.3 to 1.7 mg Fe/kg were evaluated in five healthy human male subjects as part of a phase 1 clinical study. T1-, T2-, and proton density-weighted spin-echo images as well as multiplanar gradient-echo and spoiled gradient-echo images were acquired before and 1 hour, 4 hours, and 24 hours after contrast administration. Image analysis was performed with visually selected regions of interest. Signal intensities were measured for neck lymph nodes and the adjacent muscle. Enhancement effects were evaluated as a function of dose, imaging time after contrast administration, and MR pulse sequence.RESULTSThe iron oxide particles were phagocytized by macrophages within the normal functioning lymph nodes, resulting in a dramatic decrease in signal intensity because of magnetic susceptibility effects. T2*-weighted gradient echo and T2-weighted spin echo showed significant decrease in the signal intensity of normal lymph nodes at 24 hours after contrast injection at a dose of 1.7 mg Fe/kg. No significant changes in lymph node signal intensity on T1-weighted spin-echo images were noted at any dose or imaging time point.CONCLUSIONSThis preliminary clinical evaluation demonstrates intravenous delivery of an iron-based contrast agent, resulting in negative enhancement of normal lymph nodes.     

Value of diffusion-weighted MR imaging in the differentiation between benign and malignant cervical lymph nodes

Purpose

To evaluate echo-planar diffusion-weighted MR imaging (DWI) in the differentiation between benign and malignant cervical lymph nodes.

Materials and methods

35 consecutive patients with 55 enlarged (>10 mm) cervical lymph nodes underwent MR imaging at 1.5-T. DWI was performed using a single-shot echo-planar (SSEPI) MR imaging sequence with b values (b: diffusion factor) of 0, 500 and 1000 s/mm². Apparent diffusion coefficient (ADC) maps were reconstructed for all patients and ADC values were calculated for each lymph node. Imaging results were correlated with histopathologic findings after neck dissection or surgical biopsy, findings in PET/CT or imaging follow-up. Mann-Whitney test was used for statistical analysis and a receiver operating characteristic (ROC) curve analysis was performed.

Results

Cervical lymph node enlargement was secondary to metastases from squamous cell carcinomas [n = 25], non-Hodgkin’s lymphoma [n = 6], reactive lymphadenitis [n = 20], cat scratch lymphadenitis [n = 2] and sarcoidosis [n = 2]. The mean ADC values (×10⁻³ mm²/s) were 0.78 ± 0.09 for metastatic lymph nodes, 0.64 ± 0.09 for lymphomatous nodes and 1.24 ± 0.16 for benign cervical lymph nodes. ADC values of malignant lymph nodes were significantly lower than ADC values of benign lymph nodes. 94.3% of lesions were correctly classified as benign or malignant using a threshold ADC value of 1.02 × 10⁻³ mm²/s.

Conclusion

According to our first experience, DWI using a SSEPI sequence allows reliable differentiation between benign and malignant cervical lymph nodes.     

Intravenous MR lymphography with superparamagnetic iron oxide particles: experimental studies in rats and rabbits

The inter- and intralymphonodal distribution of IV-administered superparamagnetic iron oxide (SPIO) particles as a lymphographic contrast agent for MRI was studied in various animal models in rats and rabbits. In all animals a dosage of 200 mol Fe/kg was tested. Imaging was done at 1.5 Tesla using proton-density-weighted spin-echo (PD-SE) and T2^*-weighted gradient-echo (T2^*-GRE) sequences. The time course of signal loss in popliteal lymph nodes of 21 rats was studied before and up to 72 h after IV injection of SPIO. Another 6 rats were dissected 24 h after IV injection of SPIO, all lymph nodes were embedded in agar gel and imaged ex vivo. Time course and pattern of lymph node signal loss was studied in 6 rabbits with reactive lymph node hyperplasia. The visualization of lymph node metastases was studied in 4 VX2 tumor-bearing rabbits. Most pronounced signal loss in lymph nodes was found 24 h after IV injection of SPIO with a decrease of signal in popliteal lymph nodes to 37 ± 15% (9 ± 5%) for rats and 56 ± 10% (16 ± 9%) for rabbits with the PD-SE (T2^*-GRE) sequence. Ex vivo examinations of rat lymph nodes and in vivo examinations in rabbits with lymph node hyperplasia demonstrated marked variations in contrast agent accumulation between different lymph node groups. In VX2 tumor-bearing rabbits lymph node metastases could be well delineated in postcontrast MRI if a sufficient amount of contrast agent reached the lymph nodes (2 rabbits). Inhomogeneous signal loss as well as supersaturation impeded correct lymph node assessment (2 rabbits). We conclude that IV MR lymphography using SPIO may be an approach for non invasive tumor staging, but this new technique could be limited by variations in contrast agent distribution between different lymph node groups.     

Iron oxide-enhanced MR lymphography: initial experience

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.     

Appearance of primary lymphoid malignancies on lymphotropic nanoparticle-enhanced magnetic resonance imaging using ferumoxtran-10

Patients with pathologically confirmed lymphoma/leukemia were retrospectively identified from a large single-institution phase III clinical trial with ferumoxtran-10. Five (2.3%) of 220 patients had lymphoid malignancies involving lymph nodes. A subset of patients (n=27) with biopsy-proven nodal metastases from genitourinary or breast cancer was selected as control group. Ferumoxtran-10 enhancement patterns and signal-to-noise ratios of lymph nodes involved by metastases and lymphoid malignancy were assessed. Like nodal metastases, nodes involved by lymphoid malignancies demonstrate persistent high T2*-signal intensity on lymphotropic nanoparticle-enhanced magnetic resonance imaging.