Ferumoxides-enhanced MR Imaging Research Articles

Diagnosis of Thoracic Splenosis by Ferumoxides-enhanced Magnetic Resonance Imaging

We report on a 56-year-old woman with a history of splenectomy and surgery of the left hemidiaphragm, who presented with multiple pleural and mediastinal mass lesions. On the basis of the patient's history of splenectomy and missing Howell-Jolly bodies in peripheral blood smears, splenosis was suspected. To confirm the presumptive diagnosis, ferumoxides-enhanced magnetic resonance was performed. As all lesions showed a pronounced signal loss on T2* sequences, the diagnosis of splenosis was made and was further confirmed by scintigraphy. The reported case illustrates that ferumoxides-enhanced magnetic resonance imaging may be a helpful tool for the evaluation of suspected splenosis.

Detection of hepatocellular carcinoma by ferumoxides‐enhanced MR imaging in cirrhosis: Incremental value of dynamic gadolinium‐enhancement

To investigate the incremental value of dynamic gadolinium-enhancement performed immediately after ferumoxides-enhanced magnetic resonance (MR) imaging on the detection of hepatocellular carcinoma in patients with cirrhosis. We retrospectively reviewed MR scans of 62 cirrhotic patients over a two-year period. Sequences included ferumoxides-enhanced T2-weighted fast spin echo followed by dynamic gadolinium-enhanced T1-weighted spoiled gradient echo. Two readers independently documented the presence of hepatocellular carcinoma on a three-point confidence scale, without and with gadolinium-enhanced images. The presence or absence of hepatocellular carcinoma was established by histopathology (58 patients) or follow-up imaging (four patients) over a mean period of nine months. A total of 71 hepatocellular carcinomas were found in 42 patients. There was no statistically significant difference in sensitivity for the diagnosis of hepatocellular carcinoma without vs. with gadolinium-enhanced images (68% vs. 74% for reader 1 and 62% vs. 73% for reader 2, respectively, P > 1.3). However, both readers showed a lower mean confidence for tumor detection without vs. with gadolinium-enhanced images (2.3 vs. 2.7 for reader 1, 2.3 vs. 2.9 for reader 2, P < 0.01). In our study, the addition of dynamic gadolinium-enhancement to ferumoxides-enhanced MR imaging did not improve hepatocellular carcinoma detection, but the addition of gadolinium-enhancement is recommended if ferumoxides-enhanced imaging is used because it increased reader confidence.

Detection of hepatocellular carcinoma: comparison of Gd-DTPA- and ferumoxides-enhanced MR imaging

The aim was to compare the diagnostic performance of dynamic Gd-DTPA- and ferumoxides-enhanced MRI for hepatocellular carcinoma (HCC). Twenty-five patients with chronic hepatitis or liver cirrhosis underwent both dynamic gadopentetate- and ferumoxides-enhanced MRI studies of the liver for HCC detection on the same day. MR data of both studies were retrospectively and independently analyzed. Two observers determined in consensus the grade of diffuse fibrotic liver changes (mild, moderate or severe) and the number of focal lesions. HCCs were confirmed by histology (n=22) and/or follow-up studies for at least six months (n=64). Differences in results obtained from both MR data sets were tested for significance with the McNemar's test (p<0.05). Ferumoxides-enhanced MR images detected 84 of 99 hepatic lesions, including 82 of 86 HCCs and 2 false positive, nonmalignant lesions, while Gd-DTPA-enhanced MR images detected 92 of 99 hepatic lesions, including 81 of 86 HCCs and 11 false positive, nonmalignant lesions. Sensitivity of MRI for detection of HCCs was not significantly different between ferumoxides-enhanced (95.3%; p>0.05) and Gd-DTPA-enhanced scans (94.2%). Gd-DTPA- and ferumoxides-enhanced MRI perform equally well for HCC detection. The majority of small hypervascular hepatic lesions, detected on dynamic Gd-DTPA-enhanced MRI but not on ferumoxides-enhanced MRI, represent no HCCs.

Superior mediastinal and neck lymphatic mapping in mid- and lower-thoracic esophageal cancer as defined by ferumoxides-enhanced magnetic resonance imaging

The purpose of this study was to detect lymphatic drainage into the superior mediastinum and neck in thoracic esophageal cancer patients using ferumoxides-enhanced magnetic resonance imaging (MRI), and to have this information assist in determining the appropriate extent of lymphadenectomy. Nine male patients with T2-T3 mid- and lower-thoracic esophageal cancer with lymph node metastasis were examined. The day before surgery, ferumoxides was endoscopically injected into the submucosal layer of the peritumoral lesion. Thereafter, lymph nodes in the superior mediastinum and neck, which were shown to be ferumoxides-enhanced on MRI, were harvested and evaluated; magnetic force from all harvested lymph nodes was measured ex vivo. MRI of the superior mediastinum and neck revealed 1(median) ferumoxides-enhanced lymph nodes in eight (89%) patients, and there was laterality in the lymphatic mapping in both areas. Of the 15 lymph nodes into which drainage was detected by enhanced MRI, 12 (80%) were magnetite-positive. In six patients (67%), magnetic resonance enhanced lymph nodes corresponded completely with the ex vivo magnetite examination, and in 3 patients (33%) there was partial agreement. In 3 (60%) of the 5 patients that showed paratracheal and/or supraclavicular lymph node metastases, all of the affected nodes were detected by MRI; in one patient some of the affected nodes were detected. Ferumoxides-enhanced MRI is useful for visualizing lymphatic drainage to the superior mediastinum and neck in thoracic esophageal cancer. It is an adequate procedure to form an estimate on the appropriate extent of lymphadenectomy.

Assessment of Kupffer cells by ferumoxides-enhanced MR imaging is beneficial for diagnosis of hepatocellular carcinoma: comparison of pathological diagnosis and perfusion patterns assessed by CT hepatic arteriography and CT arterioportography

To investigate the clinical significance of the radiographic assessment of Kupffer cells and hemodynamics in the diagnosis of hepatocellular nodules, both magnetic resonance (MR) imaging enhanced by ferumoxides and CT hepatic arteriography (CTHA)/CT arterioportography (CTAP) were undertaken for 118 patients with 158 primary nodular hepatocellular lesions. The radiographic findings were analyzed in the context of the pathological diagnosis. Among nodules presumed to be pre- or early HCC by CTHA/CTAP, all 13 hyperintense nodules identified by MR imaging (MRI) were found pathologically to be hepatocellular carcinoma (HCC). In contrast, in 14 hypointense nodules, no advanced (moderately or poorly differentiated) HCC was pathologically identified and none of these progressed to advanced HCC during the follow up period (mean: 24 months). Instead, 78% of these cases were pathologically confirmed as dysplastic nodules. For the 16 lesions undetectable by CTHA/CTAP, four of eight (50%) hypointense nodules turned out to be dysplastic nodules and one hyperintense lesion was HCC. Signal intensity by ferumoxides-enhanced MRI showed a strong correlation with the increase or decrease of Kupffer cells assessed by immunohistochemistry. Assessment of Kupffer cells by ferumoxides-enhanced MRI is beneficial for the accurate diagnosis of primary hepatocellular nodules that are considered borderline or early stage HCC by their hemodynamic profile.

Ferumoxides-enhanced double-echo T2-weighted MR imaging in differentiating metastases from nonsolid benign lesions of the liver.

To investigate whether ferumoxides-enhanced double-echo T2-weighted magnetic resonance (MR) imaging alone can allow differentiation of metastases from benign lesions in the noncirrhotic liver. At retrospective review of files and images, 60 lesions (22 metastases, 20 hemangiomas, and 18 cysts) were identified in 42 patients. All fast spin-echo T2-weighted MR images obtained before and after administration of ferumoxides with short (80-90 msec) and long (180-250 msec) echo times (TEs) were acquired with a 1.5-T system. Differences in lesion-to-liver signal intensity ratio between images obtained with long and short TEs were calculated. Data from all 60 lesions were entered into a receiver operating characteristic analysis. Three independent readers scored their observations of each lesion with a confidence level of 1-5. The diagnostic accuracy of each analysis method was determined by calculating the area under each reader-specific receiver operating characteristic curve. Interobserver agreement was calculated with the use of chance-corrected kappa statistics. Relative sensitivity, specificity, and accuracy of characterizing benign lesions with each method were calculated. Markedly low signal intensity and lesion-to-liver ratio on ferumoxides-enhanced images were observed with hemangioma. The difference of lesion-to-liver ratio between long and short TEs on ferumoxides-enhanced images was significantly different from that of unenhanced images and that of metastases or cysts. Interobserver agreement was good to excellent. Ferumoxides-enhanced images (with short and long TEs) showed significantly higher diagnostic accuracy than that of unenhanced images (with short or short and long TEs). Ferumoxides-enhanced images showed similar sensitivity, specificity, and accuracy when all images were reviewed together. Ferumoxides-enhanced T2-weighted MR images appear useful in differentiating metastases from benign (nonsolid) lesions in the liver.

Detection of malignant hepatic lesions before orthotopic liver transplantation: accuracy of ferumoxides-enhanced MR imaging.

The purpose of this study was to evaluate the diagnostic accuracy of ferumoxides-enhanced MR imaging for screening malignant hepatic lesions before orthotopic liver transplantation. The study comprised 48 patients who underwent MR imaging within 6 months before transplantation. Imaging techniques included unenhanced and ferumoxides-enhanced T1-weighted gradient-echo and T2-weighted fast spin-echo sequences and ferumoxides-enhanced T2(*)-weighted gradient-echo sequences. Qualitative and quantitative analyses were performed; the gold standard was the histopathologic reports of explanted livers. Twenty patients had malignant hepatic lesions, and 24 hepatocellular carcinomas were histopathologically proven. The mean area under the receiver operating characteristic curve and the mean sensitivity were significantly greater for the image sets with ferumoxides-enhanced gradient-echo sequences than for those without these sequences. The mean sensitivity and specificity of all sequences were 85% and 74% on a per-patient basis, respectively. The mean contrast-to-noise ratio was significantly greater for the ferumoxides-enhanced T2(*)-weighted gradient-echo sequences than for any other sequences and for the ferumoxides-enhanced T1-weighted gradient-echo sequences than for unenhanced sequences and the ferumoxides-enhanced T2-weighted fast spin-echo sequences. Ferumoxides-enhanced gradient-echo sequences improved the diagnostic accuracy and the sensitivity for detecting malignant hepatic lesions in patients with end-stage cirrhosis of the liver. However, the specificity was not improved even after the administration of ferumoxides because of the false-positive lesions that were mainly the result of fibrotic changes.

Characterization of focal hepatic lesions with ferumoxides-enhanced MR imaging: utility of T1-weighted spoiled gradient recalled echo images using different echo times.

To evaluate the different signal characteristics of focal hepatic lesions on ferumoxides-enhanced MR imaging, including T1-weighted spoiled gradient recalled echo (GRE) images using different echo times (TE) and T2- and T2*-weighted images. Ferumoxides-enhanced MR imaging was performed using a 1.5-T system in 46 patients who were referred for evaluation of known or suspected hepatic malignancies. One hundred and seven lesions (42 hepatocellular carcinomas [HCC], 40 metastases, 13 cysts, eight hemangiomas, three focal nodular hyperplasias [FNHs], and one cholangiocarcinoma) were evaluated. Postcontrast MR imaging included 1) T2-weighted FSE; 2) T2*-weighted GRE; 3) T1-weighted spoiled GRE using moderate (TE = 4.2-4.4 msec) TE; and 4) minimum (TE = 1.8-2.1 msec) TE. Signal intensities of the focal lesions were rated by two radiologists in conference as follows: hypointense, isointense or invisible, hyperintense, and markedly hyperintense. Lesion-to-liver contrast-to-noise ratio (C/N) was measured by one radiologist for a quantitative assessment. On ferumoxides-enhanced FSE images, 92% of cysts were "markedly hyperintense" and most of the other lesions were "hyperintense", and the mean C/N of cysts was significantly higher than that of other focal lesions. T2*-weighted GRE images showed most lesions with similar hyperintensities and the mean C/N was not significantly different between any two types of lesion. T1-weighted GRE images using moderate TE showed all FNHsand hemangiomas, 29 (69%) HCCs and eight (20%) metastases as "hyperintense". On T1-weighted GRE images using minimum TE, however, all HCCs and metastasis except one were iso- or hypointense, while all of the FNHs and hemangiomas were hyperintense. Ring enhancement was highly suggestive of malignant lesions, and was more commonly seen on the minimum TE images than on the moderate TE images. Addition of T1-weighted GRE images using minimum and moderate TE is helpful for characterizing focal lesions in ferumoxides-enhanced MR imaging.

Hepatocellular carcinoma: detection with gadolinium- and ferumoxides-enhanced MR imaging of the liver.

To test the hypothesis that the accuracy of gadolinium- and ferumoxides-enhanced magnetic resonance (MR) imaging is different in small (< or =1.5-cm) and large (>1.5-cm) hepatocellular carcinomas (HCCs). Forty-three consecutive patients with chronic liver disease were enrolled in this study. The imaging protocol included unenhanced breath-hold T1-weighted fast field-echo sequences, unenhanced respiratory-triggered T2-weighted turbo spin-echo (SE) sequences, dynamic gadolinium-enhanced T1-weighted three-dimensional turbo field-echo sequences, and ferumoxides-enhanced T2-weighted turbo SE sequences. Images of each sequence and two sets of sequences (ferumoxides set and gadolinium set) were reviewed by four observers. The ferumoxides set included unenhanced T1- and T2-weighted images and ferumoxides-enhanced T2-weighted turbo SE MR images. The gadolinium set included unenhanced T1- and T2-weighted images and dynamic gadolinium-enhanced three-dimensional turbo field-echo MR images. In receiver operating characteristic (ROC) curve analysis, the sensitivity and accuracy of the sequences were compared in regard to the detection of all, small, and large HCCs. Imaging performance was different with gadolinium- and ferumoxides-enhanced images in the detection of small and large HCCs. For detection of small HCCs, the sensitivity and accuracy with unenhanced and gadolinium-enhanced imaging (gadolinium set) were significantly (P =.017) superior to those with unenhanced and ferumoxides-enhanced imaging (ferumoxides set). The area under the composite ROC curves, or A(z), for the gadolinium set and the ferumoxides set was 0.97 and 0.81, respectively. For large HCC, the ferumoxides set was superior compared with the gadolinium set, but this difference was not statistically significant. Analysis of all HCCs demonstrated no significant differences for gadolinium- and ferumoxides-enhanced imaging. For the detection of early HCC, gadolinium-enhanced MR imaging is preferred to ferumoxides-enhanced MR imaging because the former demonstrated significantly greater accuracy in the detection of small HCCs.

Optimal pulse sequence for ferumoxides-enhanced MR imaging used in the detection of hepatocellular carcinoma: a comparative study using seven pulse sequences.

ObjectiveTo identify the optimal pulse sequence for ferumoxides-enhanced magnetic resonance (MR) imaging in the detection of hepatocelluar carcinomas (HCCs).Materials and MethodsSixteen patients with 25 HCCs underwent MR imaging following intravenous infusion of ferumoxides. All MR studies were performed on a 1.5-T MR system, using a phased-array coil. Ferumoxides (Feridex IV) at a dose of 15 µmol/Kg was slowly infused intravenously, and axial images of seven sequences were obtained 30 minutes after the end of infusion. The MR protocol included fast spin-echo (FSE) with two echo times (TR3333 8571/TE18 and 90-117), singleshot FSE (SSFSE) with two echo times (TR∞/TE39 and 98), T2*-weighted gradient-recalled acquisition in the steady state (GRASS) (TR216/TE20), T2*-weighted fast multiplanar GRASS (FMPGR) (TR130/TE8.4-9.5), and T2*-weighted fast multiplanar spoiled GRASS (FMPSPGR) (TR130/TE8.4-9.5). Contrast-to-noise ratios (CNRs) of HCCs determined during the imaging sequences formed the basis of quantitative analysis, and images were qualitatively assessed in terms of lesion conspicuity and image artifacts. The diagnostic accuracy of all sequences was assessed using receiver operating characteristic (ROC) analysis.ResultsQuantitative analysis revealed that the CNRs of T2*-weighted FMPGR and T2*-weighted FMPSPGR were significantly higher than those of the other sequences, while qualitative analysis showed that image artifacts were prominent at T2*-weighted GRASS imaging. Lesion conspicuity was statistically significantly less clear at SSFSE imaging. In term of lesion detection, T2*-weighted FMPGR, T2*-weighted FMPSPGR, and proton density FSE imaging were statistically superior to the others.ConclusionT2*-weighted FMPGR, T2*-weighted FMPSPGR, and proton density FSE appear to be the optimal pulse sequences for ferumoxides-enhanced MR imaging in the detection of HCCs.

Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides-enhanced MR imaging: importance of Kupffer cell number.

To correlate the conspicuity of hepatocellular carcinomas and dysplastic nodules on ferumoxides-enhanced magnetic resonance (MR) images with the number of Kupffer cells in the hepatic lesions, as compared with that in background liver in histopathologic findings. Sixty-nine histopathologically proved moderately or poorly differentiated hepatocellular carcinomas, 10 well-differentiated hepatocellular carcinomas, and 19 dysplastic nodules were retrospectively studied in 68 patients with cirrhosis who underwent ferumoxides-enhanced MR imaging. The contrast-to-noise ratio between the nodules and surrounding parenchyma was calculated at T2-weighted fast spin-echo imaging, and the difference in the number of Kupffer cells between the nodules and surrounding hepatic tissue was calculated histopathologically. The results of MR imaging and histopathologic examination were correlated. All 69 moderately or poorly differentiated hepatocellular carcinomas had high contrast-to-noise ratios at MR imaging and large differences in the number of Kupffer cells. Six of the 10 well-differentiated hepatocellular carcinomas had contrast-to-noise ratios of zero or nearly zero, and five of these had little difference in the number of Kupffer cells. All 19 dysplastic nodules had contrast-to-noise ratios of zero or nearly zero, and there were virtually no differences in the number of Kupffer cells. Hepatocellular nodule conspicuity at ferumoxides-enhanced MR imaging depends on differences in the number of Kupffer cells within a nodule and the surrounding cirrhotic liver; moderately or poorly differentiated hepatocellular carcinomas can be distinguished from well-differentiated hepatocellular carcinomas and dysplastic nodules.

Malignant hepatic tumor detection with ferumoxides‐enhanced MR imaging with a 1.5‐T system: Comparison of four imaging pulse sequences

The purpose of our study was to compare observer performance in the detection of malignant hepatic tumors with ferumoxides-enhanced magnetic resonance (MR) images obtained with proton density-weighted spin-echo (SE), T2-weighted fast SE, T2*-weighted gradient-recalled-echo (GRE), and proton density-weighted echo-planar (EP) sequences. Ferumoxides-enhanced MR images obtained with the four sequences in 50 patients with 92 solid malignant and 64 nonsolid benign lesions were retrospectively analyzed. Image review was conducted on a segment-by-segment basis; a total of 397 liver segments was reviewed separately for solid and nonsolid lesions by three independent readers. Observer performance was evaluated with receiver operating characteristic analysis. Lesion-to-liver contrast-to-noise ratio was higher with SE and EP than with GRE and fast SE images for solid lesions (P < 0.05), and higher with fast SE and SE than with GRE images for nonsolid lesions (P < 0.01). Proton density-weighted SE and T2-weighted fast-SE images were superior to T2*-weighted GRE and proton density-weighted EP images for detection of malignant hepatic tumors. T2-weighted fast SE images were the best for detection of nonsolid lesions. T2-weighted fast SE images that were comparable to proton density-weighted SE images for solid tumor detection, that were the best for nonsolid lesion detection, and that had an acquisition time of one third to half of that of SE imaging may be able to replace SE images for ferumoxides-enhanced liver imaging. J. Magn. Reson. Imaging 2001;13:249–257. © 2001 Wiley-Liss, Inc.

Nondiffuse fatty change of the liver: discerning pseudotumor on MR images enhanced with ferumoxides-initial observations.

To clarify the findings of nondiffuse fatty change of the liver on ferumoxides-enhanced magnetic resonance (MR) images. Of 202 patients who underwent ferumoxides-enhanced MR imaging, eight who had nondiffuse fatty change of the liver at computed tomography (CT) were examined as study subjects. MR imaging findings before and 1 hour after ferumoxides administration were compared with CT findings. Focal fatty areas of the liver showing low attenuation on CT images were depicted as areas of relatively high intensity on the ferumoxides-enhanced T1-weighted images in all patients. On enhanced T2-weighted images, focal fatty change showed relatively high intensity in three and isointensity in one of the four patients. Focal spared areas appearing as areas of relatively high attenuation on CT images were depicted as areas of relatively low intensity on the ferumoxides-enhanced T1- and T2-weighted images in all patients. Although prior reports of hepatic MR imaging with ferumoxides indicated that there is accumulation of ferumoxides within focal fatty areas that are no longer seen after the administration of contrast medium, this study revealed that focal fatty change and focal spared areas of fatty liver may be pseudotumors because of the relatively high intensity of fatty areas of the liver. Radiologists can distinguish these conditions from hepatic tumors by using the opposed-phase gradient-echo sequence or the fat-saturation technique.

Characterization of focal hepatic lesions with ferumoxides-enhanced T2-weighted MR imaging.

The purpose of this study was to evaluate whether ferumoxides-enhanced MR imaging of focal hepatic lesions provides distinctive signal intensity and lesion-to-liver contrast changes for benign and malignant lesions, helping to further characterize and differentiate these lesions. Data analysis was performed on 70 patients, with previously identified focal hepatic lesions, who underwent MR imaging of the liver before and after IV administration of ferumoxides (10 micromol Fe/kg). Lesions analyzed with pathologically proven diagnoses included metastases (n = 40), hepatocellular carcinoma (n = 11), cholangiocarcinoma (n = 6), hemangioma (n = 4), focal nodular hyperplasia (n = 6), and hepatocellular adenoma (n = 3). Response variables measured and statistically compared included the percentage of signal-intensity change and lesion-to-liver contrast. Focal nodular hyperplasia showed significant signal intensity loss on ferumoxides-enhanced T2-weighted images (mean, -43%+/-6.7%, p < 0.01). All other lesion groups showed no statistically significant change in signal intensity on ferumoxides-enhanced T2-weighted images, although signal intensity loss was seen in some individual hepatocellular adenomas (mean, -6.6%+/-24.0%) and hepatocellular carcinomas (mean, -3.3%+/-10.3%). All lesions, with the exception of hepatocellular carcinoma, had a marked increase in lesion-to-liver contrast on ferumoxides-enhanced T2-weighted images, which was statistically significant for metastases and hemangioma (p < 0.02). Focal nodular hyperplasia shows significant decrease in signal intensity on ferumoxides-enhanced T2-weighted images, which may aid in the differentiation of focal nodular hyperplasia from other focal hepatic lesions. Other lesions, namely, hepatocellular adenoma and carcinoma, can have reticuloendothelial uptake, but usually to a lesser degree than that of focal nodular hyperplasia.

Detection of colorectal liver metastases: prospective comparison of unenhanced and ferumoxides-enhanced magnetic resonance imaging at 1.5 T, dual-phase spiral CT, and spiral CT during arterial portography

Detection of colorectal liver metastases: prospective comparison of unenhanced and ferumoxides-enhanced magnetic resonance imaging at 1.5 T, dual-phase spiral CT, and spiral CT during arterial portography

Ferumoxides and Tc-99m sulfur colloid: comparison of the tumor-to-liver uptake in focal nodular hyperplasia.

The tumor-to-liver uptake of two reticuloendothelial agents, namely ferumoxides and technetium-99m (Tc-99m) sulfur colloid, was compared in focal nodular hyperplasia (FNH). Twelve patients with FNH who had undergone ferumoxides-enhanced MR imaging and planar Tc-99m sulfur colloid scintigraphy within 1 year were included from the study. Fourteen patients with FNH with a diameter larger than 3 cm were selected for the comparison. The tumor-to-liver ferumoxides uptake was calculated and the Tc-99m sulfur colloid uptake was assessed visually. Fermuoxides uptake was observed in all but one patient with FNH (mean tumor-to-liver ratio = .36). The six tumors showing normal (n = 5) or increased (n = 1) radiocolloid uptake when compared to the liver accumulated more ferumoxides than the eight tumors showing decreased radiocolloid uptake (P < .01). However, in some tumors, no direct relation was observed between ferumoxides and Tc-99m sulfur colloid uptake. Our observations suggest that ferumoxides uptake might not exactly mimic Tc-99m sulfur colloid uptake in FNH.