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.     

MR imaging of mediastinal lymph nodes: evaluation using a superparamagnetic contrast agent

The purpose of this study was to determine whether intravenous injection of a magnetic resonance (MR) contrast agent, ultrasmall superparamagnetic iron oxide (ferumoxtran-10), can be useful in characterizing lymph nodes in patients with lung cancer. Twelve patients with known or suspected lung cancer were studied. Pre- and postcontrast injection of ferumoxtran-10 MR scans of the chest were obtained. Analysis of the signal intensities and bronchoscopic fine needle aspiration of a single node were performed in each patient. Six of 12 patients had a final diagnosis of lung cancer. T1-weighted images were best for localizing mediastinal lymph nodes. Signal intensity changes before and after contrast were best visualized on T2-weighted and gradient-echo images. All four patients with lung cancer who had nodes positive for malignancy at biopsy had no change in signal intensity of the nodes on T2 images. The signal intensity decreased in the remaining two patients, and the nodes were benign. Of the eight patients with benign disease, five had no change in signal intensity of the nodes. Therefore the sensitivity for tumor involvement of the nodes is 100%, but the specificity is only 37.5%. Ferumoxtran-10 is a contrast agent that can alter the signal intensity of lymph nodes. Lack of signal change may be due to malignant or inflammatory change. Studies in a larger population of lung cancer patients may help to characterize the utility of this agent further. J. Magn. Reson. Imaging 2000;12:899-904.     

USPIO-enhanced magnetic resonance imaging for nodal staging in patients with head and neck cancer

PURPOSE: To determine the accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for nodal staging in patients with head and neck cancer. MATERIALS AND METHODS: Twenty patients with carcinomas of the upper aerodigestive tract were prospectively enrolled. MRI was performed before and 24-36 hours after intravenous infusion of an USPIO agent, ferumoxtran-10 (Sinerem; Guerbet, France; and Combidex; Advanced Magnetics) at a dose of 2.6 mg Fe/kg using T2-weighted spin-echo and gradient-echo sequences. Surgery was performed the same day or the day after the ferumoxtran-10-enhanced MR examination. Based on MRI, selected nodes were surgically removed and directly correlated with pathology using hematoxylin-eosin (H&E) and Perls stainings. RESULTS: A total of 63 nodes were studied; 36 were nonmetastatic, 25 metastatic, and two inflammatory. Ferumoxtran-10-enhanced MRI allowed diagnosis of 24 metastatic and 30 nonmetastatic nodes, yielding a sensitivity of 96%, a specificity of 78.9%, a positive predictive value of 75%, and a negative predictive value of 96.8%, compared to 64%, 78.9%, 66.6%, and 76.9%, respectively, for nonenhanced MRI. Accuracy of ferumoxtran-10-enhanced MRI was 85.7%. The gradient-echo T2-weighted sequence was the most accurate to detect signal loss in nonmetastatic nodes. CONCLUSION: USPIO-enhanced MRI is useful for nodal staging of patients with head and neck cancers.     

Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide

PURPOSE: To evaluate a new ultrasmall superparamagnetic particles of iron oxide (USPIO) compound, ferumoxytol, as a marker of macrophage activity in atherosclerotic plaques and to compare it to ferumoxtran-10. MATERIALS AND METHODS: Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits served as the animal model for atherosclerosis, four coeval female New Zealand White (NZW) rabbits were the control group. Five WHHL and two NZW received a single intravenous injection (250 micromol/kg) of either ferumoxtran-10 or ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body scanner for the next five days. Development of signal intensity changes and susceptibility effects was assessed. Statistical analysis was based on a nonparametric Wilcoxon-Mann-Whitney-U test by using a P value at the 0.05 significance level. On day 5, the rabbits were sacrificed and the aorta was referred to histopathology, distribution of iron particles in the vessel wall was analyzed. RESULTS: MRI was feasible in all animals. Three days after injection of ferumoxytol the highest luminal signal intensity measurements were observed in the ferumoxytol group; the highest measurements were five days after injection in the ferumoxtran-10 group (P < 0.05). In the WHHL, susceptibility effects presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol and spotted areas void of signal after ferumoxtran-10. None of these findings were observed in the NZW control groups. CONCLUSION: Ferumoxtran-10 and ferumoxytol at a respective dose of 250 mumol/kg appear well suited for atherosclerotic plaque detection with MRI in experimental atherosclerosis. Ferumoxytol warrants further analysis in humans.     

Splenic imaging with ultrasmall superparamagnetic iron oxide ferumoxtran-10 (AMI-7227): preliminary observations

PURPOSE: Ferumoxtran-10 (ultrasmall superparamagnetic iron oxide; Combidex, AMI-7227) is a long-circulating MR contrast agent with reticuloendothelial uptake known to enhance tissue T1 and T2 relaxation rates. The purpose of this study was to assess the effect of ferumoxtran-10-enhanced MRI in evaluating focal splenic lesions. METHOD: Eighteen patients underwent MR evaluation of the spleen. Two of these patients with exophytic normal splenic tissue (splenules) and 13 of these patients with 24 focal splenic lesions (7 cysts, 2 hemangiomas, 7 metastases, 1 infarct, 7 lymphoma) were assessed by T1-weighted gradient echo and T2-weighted fast SE MRI following intravenous administration of ferumoxtran-10 (1.1 mg of Fe/kg). Qualitative analysis involving improved lesion detection and/or characterization, additional information from postcontrast images affecting staging, and patient management was performed. Quantitative measurements of lesion-to-spleen contrast-to-noise ratio were also performed. RESULTS: Additional information was provided by ferumoxtran-10-enhanced images in 15 of 18 patients. In 8 of 15 (53%) patients, improved lesion detection (i.e., number of lesions) was obtained on contrast-enhanced images. Improved lesion visualization (i.e., conspicuity) was noted in 11 of 15 (73%) of patients. In 10 of 15 (67%) patients, postcontrast imaging provided additional information leading to lesion characterization. Staging of disease and patient management were affected in 5 of 15 (33%) and 6 of 15 (40%) patients, respectively. CONCLUSION: Ferumoxtran-10 is a promising contrast agent for the evaluation of focal splenic lesions.     

Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization?

OBJECTIVE: Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS: Seventy-seven patients (58 men, 19 women) with proven primary cancer (bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at l.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was performed separately for both reviewers. RESULTS: Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z) = area under ROC curve] reviewer 1, A(z) = 0.92; reviewer 2, A(z) = 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z) = 0.94; reviewer 2, A(z) = 0.93) showed a statistically significant difference (p = 0.01) for reviewer 1 but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION: On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization. However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone.     

Differential uptake of ferumoxtran-10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: critical determinants of atherosclerotic plaque labeling

PURPOSE: To compare atherosclerotic plaque uptake of a first (ferumoxtran-10) and second generation (ferumoxytol) ultrasmall superparamagnetic iron oxide (USPIO) contrast agent with different pharmacokinetic/pharmacodynamic properties. MATERIALS AND METHODS: New Zealand White rabbits maintained on a high cholesterol/fat diet were subjected to balloon injury to the abdominal aorta. Ferumoxtran-10 or ferumoxytol (500 micromol/kg) was administered at 2, 4, and 8 weeks following injury. In vivo magnetic resonance imaging (MRI) was performed immediately prior to, immediately after, and 6 days post-contrast administration. Ex vivo MRI, histologic, and inductively coupled plasma-mass spectrometry (ICP-MS) iron analyses were performed on the excised vessels. RESULTS: The blood pool clearance of ferumoxytol (t(1/2) < or = 6 hours) was more rapid than that of ferumoxtran-10 (t(1/2) < or = 48 hours). Decreased in vivo MRI signal intensity in the abdominal aorta was observed at 2, 4, and 8 weeks following injury with ferumoxtran-10, but not with ferumoxytol. Consistent with these observations, ex vivo MRI signal intensity was decreased in the ferumoxtran-10 vessels, and to a lesser degree in the ferumoxytol vs. control vessels (- contrast agent). In contrast, in vitro macrophage phagocytosis of USPIO was four to six fold greater with ferumoxytol than with ferumoxtran-10. Additionally, the absolute iron content correlated with ex vivo MRI signal intensity in all vessels (r = -0.86, P < 0.0001). CONCLUSIONS: These data suggest that the exposure period of atherosclerotic plaque to USPIO rather than the kinetics of the USPIO uptake by plaque alone is a critical criterion for experimental design of in vivo studies.     

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data

The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period. There were no clinically significant effects on vital signs, physical examination, and laboratory results. Ferumoxtran-10 is a safe and well tolerated MR contrast agent.     

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.     

Pelvic lymph node visualization with MR imaging using local administration of ultra-small superparamagnetic iron oxide contrast

PURPOSE: To determine if interstitial injection of iron oxide particles improves visualization of pelvic lymph nodes at magnetic resonance imaging (MRI) and to determine the effect of injection site on location of visualized nodes. MATERIALS AND METHODS: In nine healthy volunteers, ferumoxtran-10 iron oxide (0.28 mg iron per kg) was injected into the anterior thigh (three subjects) or perianal (three subjects) or periprostatic tissues (three subjects). MRI at 1.5 T was performed before injection and one, three, and seven days after injection. RESULTS: The mean of 30 nodes seen post-injection was greater than the mean of 5.8 seen pre-injection (P < 0.001). After thigh injection, a mean of three internal vs. 36 external nodes were seen. Compared with thigh injection, there was a higher fraction of internal nodes with perianal (mean of nine internal vs. 14 external, P < 0.001) and periprostatic injection (mean of 11 internal vs. five external, P < 0.001). More nodes were seen with gradient-echo sequences than with other sequences (P < 0.001). CONCLUSION: Interstitial injection of iron oxide particles increases visualization of pelvic lymph nodes. Perianal and periprostatic injection increases the number of internal pelvic lymph nodes seen compared with thigh injection.     

An exploratory study of ferumoxtran-10 nanoparticles as a blood-brain barrier imaging agent targeting phagocytic cells in CNS inflammatory lesions

BACKGROUND AND PURPOSE: Iron oxide-based contrast agents have been investigated as more specific MR imaging agents for central nervous system (CNS) inflammation. Ferumoxtran-10 is a virus-size nanoparticle, taken up by reactive cells, that allows visualization of the phagocytic components of CNS lesions. Ferumoxtran-10 was compared with standard gadolinium-enhanced MR images in this exploratory trial to assess its potential in evaluation of CNS lesions with inflammatory aspects, including lymphoma, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and vascular lesions. METHODS: Twenty-three patients with different types of intracranial "inflammatory" lesions underwent standard brain MR with and without gadolinium, followed an average of 10 days later by a ferumoxtran-10 scan. Patients were imaged 24 hours after infusion of 2.6 mg/kg ferumoxtran-10. All MR images were evaluated subjectively by 4 investigators for a difference in enhancement patterns, which could be useful in differential diagnoses. RESULTS: In 5 cases, (one ADEM, 2 stroke, one cavernous venous vascular malformation, one primary central nervous lymphoma) the ferumoxtran-10 scan showed higher signal intensity, larger area of enhancement, or new enhancing areas compared with gadolinium. Most MS patients showed less enhancement with ferumoxtran-10 than with gadolinium. CONCLUSION: Ferumoxtran-10 showed different enhancement patterns in a variety of CNS lesions with inflammatory components in comparison to gadolinium. The impact of timing and therapy need further evaluation to better assess ferumoxtran-10 in addition to gadolinium as contrast agents for use in diagnosis and monitoring therapy in patients with CNS inflammatory lesions.     

Single-dose contrast agent for intraoperative MR imaging of intrinsic brain tumors by using ferumoxtran-10

BACKGROUND AND PURPOSE: Intraoperative MR imaging (IMRI) has advantages over conventional framed and frameless techniques. IMRI, however, also has some drawbacks, especially related to interpretation of gadolinium-enhanced intraoperative imaging resulting from surgically induced blood brain barrier injury, vascular changes, and hemorrhage. Ultra-small superparamagnetic iron particles like ferumoxtran-10 have a long plasma half-life and are trapped by reactive cells within the tumor. These trapped particles provide a method to demonstrate enhancing lesions without the artifact of repeat gadolinium administration in the face of blood brain barrier and vascular injury. METHODS: We present a review of the literature and the cases of two patients who underwent surgery in which IMRI with ferumoxtran-10 was used. RESULTS: Ultra-small superparamagnetic iron particles represent a method to demonstrate enhancing intrinsic brain tumors without the drawbacks of intraoperative gadolinium enhancement. These lesions appear even on low-field strength IMRI. Ferumoxtran-10, administered preoperatively, provides a stable imaging marker, even after surgical manipulation of the brain. CONCLUSION: Fermumoxtran-10 provides a way to lessen artifactual enhancement during IMRI related to the administration of gadolinium.     

A preliminary study on MR lymphography with iron chondroitin sulfate colloid

We investigated MR lymphography with iron chondroitin sulfate colloid, which was an intravenous agent for iron deficiency anemia. MR images (SE350/30) of the medial iliac lymph nodes were obtained before and after subcutaneous++ injection of this agent (2 mg Fe) on dorsal hindfeet bilaterally in five rabbits (3.0 kg weight). Signal intensities of the nodes were increased 5-15 minutes after the injection and the nodes were clearly identified in three of them. In the other two, increase in the signal intensity was not shown and any nodes could not be detected macroscopically at the investigated region on dissection. These results indicated the possibility of positive contrast enhancement of lymph nodes on MR imaging using iron colloid.     

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.     

Positive contrast MR-lymphography using inversion recovery with ON-resonant water suppression (IRON)

PURPOSE: To investigate the utility of inversion recovery with ON-resonant water suppression (IRON) to create positive signal in normal lymph nodes after injection of superparamagnetic nanoparticles. MATERIALS AND METHODS: Experiments were conducted on six rabbits, which received a single bolus injection of 80 mumol Fe/kg monocrystalline iron oxide nanoparticle (MION-47). Magnetic resonance imaging (MRI) was performed at baseline, 1 day, and 3 days after MION-47 injection using conventional T(1)- and T(2)*-weighted sequences and IRON. Contrast-to-noise ratios (CNR) were measured in blood and in paraaortic lymph nodes. RESULTS: On T(2)*-weighted images, as expected, signal attenuation was observed in areas of paraaortic lymph nodes after MION-47 injection. However, using IRON the paraaortic lymph nodes exhibited very high contrast enhancement, which remained 3 days after injection. CNR with IRON was 2.2 +/- 0.8 at baseline, increased markedly 1 day after injection (23.5 +/- 5.4, P < 0.01 vs. baseline), and remained high after 3 days (21.8 +/- 5.7, *P < 0.01 vs. baseline). CNR was also high in blood 1 day after injection (42.7 +/- 7.2 vs. 1.8 +/- 0.7 at baseline, P < 0.01) but approached baseline after 3 days (1.9 +/- 1.4, P = NS vs. baseline). CONCLUSION: IRON in conjunction with superparamagnetic nanoparticles can be used to perform 'positive contrast' MR-lymphography, particularly 3 days after injection of the contrast agent, when signal is no longer visible within blood vessels. The proposed method may have potential as an adjunct for nodal staging in cancer screening.     

Prostate cancer evaluated with ferumoxtran-10-enhanced T2*-weighted MR Imaging at 1.5 and 3.0 T: early experience

PURPOSE: To prospectively evaluate the feasibility of ferumoxtran-10-enhanced magnetic resonance (MR) imaging at high magnetic field strength (3.0 T) and to compare image quality between 1.5- and 3.0-T MR imaging in terms of lymph node detection in patients with prostate cancer. MATERIALS AND METHODS: This study was institutional review board approved, and all patients gave written informed consent. Forty-eight consecutive patients aged 51-79 years (mean, 65.5 years) with prostate cancer were enrolled. T2*-weighted 1.5- and 3.0-T MR images of the pelvis were acquired in a sagittal plane parallel to the psoas muscle 24 hours after ferumoxtran-10 administration. A pelvic and body phased-array coil was used and yielded an in-plane resolution of 0.56 x 0.56 x 3.00 mm at 1.5 T and 0.50 x 0.50 x 2.50 mm at 3.0 T. All images were evaluated by three readers for total image quality, lymph node border delineation, muscle-fat contrast, and vessel-fat contrast. Statistical significance was calculated by using the Mann-Whitney U test. Subsequently, the general linear mixed model was used to estimate the contributions of three factors-patient, reader, and technique-to the variability of the imaging results. RESULTS: Significantly (P < .05) better muscle-fat contrast, vessel-fat contrast, lymph node border delineation, and total image quality were observed at 3.0-T MR imaging. The general linear mixed model revealed that the variability of all results could be attributed to the use of 3.0-T imaging. CONCLUSION: Ferumoxtran-10-enhanced MR imaging can be performed at high magnetic field strengths and result in improved image quality, which may lead to improved detection of small positive lymph nodes.     

Ferumoxtran-10, a superparamagnetic iron oxide as a magnetic resonance enhancement agent for imaging lymph nodes: a phase 2 dose study

BACKGROUND AND PURPOSE: Dextran-coated ultrasmall superparamagnetic iron oxide ferumoxtran-10 (Combidex) is used in reticuloendothelial MR imaging. Our purpose was to determine the optimal dose and imaging time for lymph node evaluation. MATERIALS: Twenty-four healthy volunteers underwent neck MR imaging before and 6, 12, 24, and 36 hours after receiving 1.1, 1.7, 2.6, or 3.4 mg Fe/kg ferumoxtran-10. Vital signs, serum and urine levels, and adverse events were monitored. Qualitative nodal architecture, size, and signal-intensity changes were assessed on T1-, T2-, and T2*-weighted (fast field-echo 25 degrees or 80 degrees flip angle [FFE-25 or FFE-80]) images. Region-of-interest intensities were measured quantitatively. RESULTS: Consistently strong enhancement in normal nodes was found with 24- and 36-hour T2- and T2*-weighted imaging after 2.6 and 3.4 mg Fe/kg doses. No serious adverse events occurred. With 2.6 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 100% and 100% (vs 88% and 88%) with T2-weighted, 96% and 96% (vs 73% and 85%) with FFE-25, and 100% and 92% (vs 85% and 88%) with FFE-80 sequences. With 3.4 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 89% and 79% (vs 75% and 75%) with T2-weighted, 84% and 79% (vs 95% and 100%) with FFE-25, and 95% and 79% (vs 95% and 80%) with FFE-80 sequences. CONCLUSION: Ferumoxtran-10 nodal imaging appears to be effective and safe. Signal intensity and specificity for normal nodes were best 24 or 36 hours after 2.6 and 3.4 mg Fe/kg doses. Nodal conspicuity was best with T2- and T2*-weighted sequences.     

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.     

Ferumoxtran-10-enhanced MR imaging of the bone marrow before and after conditioning therapy in patients with non-Hodgkin lymphomas

To quantify permeability changes of the “blood–bone marrow barrier” (BMB) and to detect malignant bone marrow infiltrations before and after conditioning therapy for subsequent leukapheresis using ferumoxtran-10-enhanced magnetic resonance (MR) imaging. Twenty-two patients with malignant non-Hodgkin lymphomas (NHL), including 9 patients (group A) before and 13 patients (group B) after conditioning therapy, underwent MR of the spine before and after infusion of ferumoxtran-10 (0.045 mmol Fe/kg BW). Pulse sequences comprised dynamic T1-GE and pre- and post-contrast T1-SE and STIR sequences. Dynamic ΔSI-data were correlated with the quantity of mobilized CD34+ cells. In addition, the number of focal bone marrow lesions was compared before and after ferumoxtran-10 administration. Dynamic ΔSI-data were higher in group B than in group A, indicating an increased BMB permeability after conditioning therapy. However, ΔSI-data did not correlate with the quantity of mobilized CD34+ cells. Ferumoxtran-10-enhanced STIR images demonstrated a significant signal decline of the normal, non-neoplastic bone marrow and a significantly increased detection of focal neoplastic lesions compared to pre-contrast images (P<0.05). Ferumoxtran-10 depicted the bone marrow response to conditioning therapy by an increase in BMB-permeability, which, however, did not correlate with the number of mobilized CD34+ cells. Ferumoxtran-10 improved the detection of focal bone marrow lesions significantly (P<0.05).     

Interstitial MR lymphography with MS-325: characterization of normal and tumor-invaded lymph nodes in a rabbit model

OBJECTIVE: The aim of our study was to evaluate the performance of a new blood-pool contrast agent, MS-325, in depicting regional lymph nodes when injected interstitially and in allowing the subsequent classification of the lymph nodes as normal or tumor-bearing (VX2 tumor). MATERIALS AND METHODS: Six New Zealand white rabbits underwent adapted fast three-dimensional (3D) MR imaging before implantation of VX2 tumor cells in the flank and again 3 weeks after the implantation. For each imaging session, 0.5 mL of undiluted MS-325 was injected subcutaneously into both dorsal foot pads. For more than 120 min, the rabbits underwent repeated 3D MR imaging. The size of the individual lymph nodes and the amount of contrast agent uptake in the nodes were measured 5, 10, 15, 30, 60, and 120 min after the injection. After the rabbits had been sacrificed, their lymph nodes were removed and histopathologically analyzed. RESULTS. In normal as well as tumor-bearing hindlegs, the subcutaneous administration of MS-325 resulted in rapid delineation of popliteal, inguinal, iliac, and paraaortal lymph nodes. Tumor invasion into lymph nodes presented as circumscribed signal voids in the areas infiltrated by tumor, whereas the surrounding residual lymphatic tissue showed enhancement identical to that of normal nodes. CONCLUSION: In addition to providing a safe means of displaying the normal lymphatic system, MS-325-enhanced 3D MR lymphography depicts direct tumor invasion in lymph nodes.