Focal hepatic lesions: detection and characterization with combination gadolinium- and superparamagnetic iron oxide-enhanced MR imaging

PURPOSE: To compare gadolinium- and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging for detection and characterization of focal hepatic lesions when different contrast agent administration sequences are used. MATERIALS AND METHODS: Unenhanced, dynamic gadolinium-enhanced, and SPIO-enhanced hepatic MR images were obtained in 134 patients. SPIO-enhanced MR imaging was performed immediately after gadolinium-enhanced dynamic MR imaging in 50 patients, 1 day after gadolinium-enhanced dynamic MR imaging in 40 patients, and before gadolinium-enhanced dynamic MR imaging in 44 patients. Two radiologists independently reviewed the gadolinium image set (unenhanced and gadolinium-enhanced dynamic MR images) and the SPIO image set (unenhanced and SPIO-enhanced MR images) in random order. Lesion detection sensitivity and lesion characterization accuracy were compared by analyzing the area under the receiver operating characteristic curve (Az). RESULTS: Overall lesion detection accuracy for pooled data was significantly higher with the SPIO set (Az = 0.903) than with the gadolinium set (Az = 0.857) (P <.05). When hypovascular lesions were excluded, the detection rate was similar with the two sets. When hepatocellular carcinomas were excluded, the detection rate was significantly higher with the SPIO set (P <.01). Readers were more accurate in differentiating benign from malignant lesions with the gadolinium set (Az = 0.915) than with the SPIO set (Az = 0.847) (P <.01). Detection accuracy tended to be better with the images obtained after the second contrast agent was used. CONCLUSION: Hypovascular lesion detection was better with SPIO-enhanced MR images than with gadolinium-enhanced MR images. Detection and characterization of hypervascular lesions were improved with gadolinium-enhanced MR images.     

Early detection of radiation-induced liver injury in rat by superparamagnetic iron oxide-enhanced MR imaging

The detectability of early liver injury induced by irradiation was studied using magnetic resonance (MR) imaging enhanced with superparamagnetic iron oxide (SPIO), a tissue-specific contrast agent against the reticuloendothelial system (RES). In rat, 3 days after focal irradiation (0-10 Gy), MR imaging was performed and specimens were obtained to observe the phagocytic function of RES. The irradiated portion of the liver was visualized with a clear demarcation from the nonirradiated part by SPIO-enhanced MR images as a decrease in negative enhancement reflecting the function of RES (P < 0.05), whereas this was impossible with nonenhanced MR images. Significant regression was observed as a dose-related change of the signal intensity in the irradiated portion on SPIO-enhanced MR images (R = 0.867, P < 0.0001). SPIO-enhanced MR imaging was reliable for detecting the range and extent of liver injury a few days after low-dose irradiation, and it may be a useful procedure for verifying the target area in clinical cases of radiation therapy.     

Three-dimensional dynamic liver MR imaging using sensitivity encoding for detection of hepatocellular carcinomas: comparison with superparamagnetic iron oxide-enhanced mr imaging

PURPOSE: To assess the diagnostic performance of three-dimensional dynamic liver imaging with sensitivity encoding (SENSE), including double arterial phase images and increased resolution, by comparing it to superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging for the detection of hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-seven consecutive patients with 50 HCCs underwent Gd-BOPTA-enhanced dynamic imaging using SENSE and SPIO-enhanced MR imaging with at least a 24-hour interval between examinations. Using a three-dimensional gradient-echo technique applying SENSE, dynamic imaging consisting of double arterial phase-, portal phase- and delayed phase-images, was obtained. Using T2-weighted turbo spin-echo and T2*-weighted fast imaging with steady-state precession sequence, SPIO-enhanced MR imaging was obtained. For qualitative analysis, the diagnostic accuracy of both MR examinations for detecting the 50 HCCs was evaluated using the alternative free-response receiver operating characteristic method. Sensitivity and positive predictive value were also evaluated. RESULTS: The mean sensitivity and positive predictive value of three-dimensional dynamic imaging with SENSE were 91.3% and 89.2%, respectively, and those of SPIO-enhanced imaging were 77.3% and 92.6 %, respectively. There was a significant difference in sensitivity between the two images (P <0.05). The mean Az value of three-dimensional dynamic imaging with SENSE (0.97 +/- 0.01) was significantly higher than that of SPIO-enhanced imaging (0.90 +/- 0.02) (P=0.00). CONCLUSION: Three-dimensional dynamic liver MR imaging using SENSE for acquiring double arterial phase images is more efficient than SPIO-enhanced MR imaging for detecting HCCs.     

Detection of liver metastases: gadobenate dimeglumine-enhanced three-dimensional dynamic phases and one-hour delayed phase MR imaging versus superparamagnetic iron oxide-enhanced MR imaging

The aim of this study was to compare the diagnostic performance of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging, including dynamic phases and one-hour delayed phase, versus superparamagnetic iron oxide (SPIO)-enhanced imaging for detection of liver metastases. Twenty-three patients with 59 liver metastases underwent Gd-BOPTA-enhanced MR imaging (unenhanced, arterial, portal, equilibrium and one-hour delayed phase) using three-dimensional volumetric interpolated imaging and SPIO-enhanced T2-weighted turbo spin–echo and T2*-weighted gradient-echo sequences on a 1.5-T unit. Three observers independently interpreted the three sets of images, i.e. Gd-BOPTA-enhanced dynamic MRI (set 1), delayed phase imaging (set 2) and SPIO-enhanced MRI (set 3). Diagnostic accuracy was evaluated using the alternative-free response receiver operating chracteristic (ROC) analysis. Sensitivity and positive predictive value were also evaluated. The mean accuracy (Az values) and sensitivity of Gd-BOPTA-enhanced delayed phase imaging (0.982, 95.5%) were comparable to those of SPIO-enhanced imaging (0.984, 97.2%). In addition, Az values and sensitivities of both imaging sets were significantly higher than those of Gd-BOPTA-enhanced dynamic images (0.826, 77.4%: p<0.05). There was no significant difference in the positive predictive value among the three image sets. Gd-BOPTA-enhanced delayed phase imaging showed comparable diagnostic performance to SPIO-enhanced imaging for the detection of liver metastases, and had a better diagnostic performance than Gd-BOPTA-enhanced dynamic images.     

大鼠种植型肝癌的超顺磁性的氧化铁磁共振增强实验研究

目的 研究正常大鼠的超顺磁性氧化铁（ＳＰＩＯ）剂量梯度－肝脏信号曲线、大鼠种植地癌ＳＰＩＯ增强前后的对比噪声比和检出率。方法 第１组：７２只正常ＳＤ大鼠随机分成１８个样本组,平扫后以０、２、５……２８０ｕｍｏｌＦｅ／ｋｇ１８个ＳＰＩＯ剂量分别做增强扫描,做剂量梯度－肝脏信号曲线。第２组：３８只种植型肝癌模型鼠,共计生成４３个肿瘤,行平扫及ＳＰＩＯ增强扫描,分析肿瘤磁共振强化特点;测量增强前后Ｔ１及     

Hepatic lesion detection: comparison of MR imaging after the administration of superparamagnetic iron oxide with dual-phase CT by using alternative-free response receiver operating characteristic analysis

PURPOSE: To compare the performance of magnetic resonance (MR) imaging after the administration of superparamagnetic iron oxide (SPIO) and dual-phase computed tomography (CT) in the depiction of liver metastases. MATERIALS AND METHODS: Fifty-one hepatic resection candidates with known colorectal metastases were examined. MR imaging comprised fast spin-echo (SE) T2-weighted imaging, T1-weighted gradient-echo (GRE) fast low-angle shot imaging before SPIO enhancement, dual-echo SE imaging, T2-weighted fast low-angle shot imaging, and T1-weighted GRE imaging after SPIO enhancement. CT was performed with 8-mm collimation and 1:1 pitch; imaging commenced 20 seconds and 65-70 seconds after injection of 150 mL of contrast medium. All images were reviewed independently by four blinded observers. The alternative-free response receiver operating characteristic (ROC) method was used to analyze the results, which were correlated with findings from surgery, intraoperative ultrasonography, and histopathologic studies in 31 patients and with consensus review together with all other imaging and clinical follow-up in 20 patients. Sensitivities were also calculated. RESULTS: The mean sensitivity of MR was significantly higher than that of CT (p < .02): 79.8% for MR and 75.3% for CT for all lesions, and 80.6% for MR and 73.5% for CT for malignant lesions. The mean areas under the alternative-free response ROC curves were 0.83 for MR and 0.78 for CT (difference not significant). CONCLUSION: SPIO-enhanced MR imaging was more sensitive than dual-phase CT in the depiction of colorectal metastases.     

Detection and characterization of focal hepatic lesions: mangafodipir vs. superparamagnetic iron oxide-enhanced magnetic resonance imaging

PURPOSE: To compare the mangafodipir-enhanced magnetic resonance (MR) and superparamagnetic iron oxide (SPIO)-enhanced images for their ability to detect and characterize focal hepatic lesions. MATERIALS AND METHODS: Unenhanced, mangafodipir-enhanced, and SPIO-enhanced hepatic MR images obtained from 64 patients were analyzed. A total of 121 hepatic lesions were included: 66 hepatocellular carcinomas (HCCs), 26 metastases, 14 hemangiomas, 5 cysts, 3 cholangiocarcinomas, 4 focal nodular hyperplasias (FNHs), 2 abscesses, and 1 adenoma. Two radiologists independently reviewed the two sets of images in a random order: 1) the unenhanced and mangafodipir-enhanced images (the mangafodipir set) and 2) the unenhanced and SPIO-enhanced images (the SPIO set). This study compared the accuracy of lesion detection, the ability to distinguish between a benign and malignant lesion, and the ability to distinguish between the hepatocellular and nonhepatocellular origins of the lesions using the areas (Az) under the receiver operating characteristic (ROC) curve. RESULTS: The overall accuracy for detecting focal lesions was significantly higher (P < 0.05) with the SPIO set (Az = 0.846 and 0.871 for readers 1 and 2, respectively) than with the mangafodipir set (Az = 0.716 and 0.766). Most of the lesions detected only with the SPIO-enhanced MR images by the readers were small HCCs. For lesions larger than 15 mm, the sensitivities of the two contrast enhancement techniques were similar for both readers. The accuracy of the mangafodipir and SPIO sets in distinguishing between benign and malignant lesions was comparable. The accuracy for distinguishing between the hepatocellular and nonhepatocellular origins of the lesions was significantly higher (P < 0.05) using the mangafodipir set (Az = 0.897 and 0.946) than using the SPIO set (Az = 0.741 and 0.833). CONCLUSION: SPIO- and mangafodipir-enhanced images were comparable for detection of focal hepatic lesions other than small HCCs, which were better detected on the SPIO-enhanced images. Mangafodipir-enhanced images are likely better than the SPIO-enhanced images for distinguishing between focal liver lesions with a hepatocellular or nonhepatocellular origin.     

Superparamagnetic iron oxide-enhanced MR imaging: pulse sequence optimization for detection of liver cancer

The effects of magnetic resonance (MR) pulse sequences and timing parameters on tumor-liver contrast were studied in an animal model of metastatic liver cancer. Six spin-echo (SE), three inversion-recovery (IR), and four gradient-echo (GRE) sequences were evaluated at 0.6 T before and after injection of super-paramagnetic iron oxide. GRE techniques, irrespective of echo time and flip angle, showed the greatest change in signal intensity (enhancement) of the liver after administration of iron oxide. Single-acquisition GRE sequences (16 seconds) matched the contrast-to-noise ratio (C/N) performance of the most effective 6.4-minute SE sequences. Multiexcitation GRE sequences showed tumor-liver C/Ns per unit time that were significantly (P less than .05) higher than those achieved with SE and IR sequences. GRE sequences, which recruit intravoxel dephasing as an additional source of transverse relaxation enhancement (T2*), show a higher C/N per unit time and in this respect seem superior to SE and IR sequences for MR imaging with superparamagnetic iron oxide.     

Lymph node metastasis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging versus PET/CT in a rabbit model

PURPOSE: To prospectively compare the diagnostic accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging and integrated positron emission tomography-computed tomography (PET/CT) for the depiction of lymph node metastasis in an animal model, with histologic findings as the reference standard. MATERIALS AND METHODS: This experiment was approved by the local animal care committee. VX2 carcinoma was implanted into the thighs of 11 rabbits 4 weeks before the imaging study. T2- and T2*-weighted MR examinations were performed 24 hours after USPIO administration, followed by integrated PET/CT. USPIO-enhanced MR imaging and PET/CT analysis for the evaluation of the presence of metastasis in iliac lymph nodes were performed independently by two radiologists and two nuclear medicine physicians, respectively, without histopathologic knowledge. Results were evaluated by using receiver operating characteristic (ROC) analysis, and sensitivities and specificities were compared by using a Z test. RESULTS: Metastases were histopathologically confirmed in 22 of 62 iliac lymph nodes. USPIO-enhanced MR imaging showed a significantly greater area under the ROC curve than did PET/CT (0.984 vs 0.852; P=.023). The respective sensitivity and specificity for the detection of lymph node metastasis were 91% (20 of 22) and 95% (38 of 40) for USPIO-enhanced MR imaging and 64% (14 of 22) and 98% (39 of 40) for PET/CT. In terms of sensitivity, a significant difference was found between USPIO-enhanced MR imaging and PET/CT, particularly for nodal metastasis of less than 5 mm (86% [six of seven] vs 0% [zero of seven]; P=.031), whereas the specificity of the two imaging modalities was similar (P=.226). CONCLUSION: USPIO-enhanced MR imaging results in higher diagnostic accuracy for depicting lymph node metastasis than does PET/CT.     

Detection of hepatic metastases: comparison of contrast-enhanced CT, unenhanced MR imaging, and iron oxide-enhanced MR imaging

Diagnostic accuracy of contrast-enhanced CT, unenhanced MR imaging, and MR images enhanced with superparamagnetic iron oxide was evaluated in 10 patients with histologically proved hepatic metastases. First, diagnostic performance of the imaging technique with respect to the ability of radiologists to recognize the presence or absence of a metastasis was measured by using receiver-operating-characteristic (ROC) analysis of single images. Second, the total number of lesions (N = 108) detected by "complete" CT and MR examinations was counted. Finally, lesion-liver contrast-to-noise ratios (CNR) were measured in all MR sequences. The area under the ROC curve was .67 +/- .03 for contrast-enhanced CT, .81 +/- .07 for the unenhanced SE 260/14 sequence, and .92 +/- .01 for the iron oxide-enhanced SE 1500/40 sequence. The enhanced SE 1500/40 sequence yielded significantly (p less than .005) greater accuracy than did contrast-enhanced CT. The same sequence detected significantly (p less than .05) more lesions than all other imaging techniques (19% more than the best unenhanced MR sequence and 36% more than contrast-enhanced CT). The enhanced SE 1500/40 sequence also yielded the highest CNR value (19.5 +/- 10.2) of all MR sequences. These results indicate that iron oxide-enhanced MR imaging is a superior imaging technique for the detection of hepatic lesions.     

Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging

PURPOSE: To evaluate intravenously administered ultrasmall superparamagnetic iron oxide (USPIO) as a marker of macrophage activity in an experimental rabbit model of antigen-induced arthritis. MATERIALS AND METHODS: Unilateral arthritis was induced by means of intraarticular injection of methylated bovine serum albumin in 10 knees of 10 rabbits that had been presensitized to the same antigen. The contralateral knees in these rabbits, as well as six knees in three other rabbits, served as controls. After onset of arthritis, all knees were imaged prior to and 24 hours after administration of USPIO. The magnetic resonance (MR) imaging protocol included T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo, and short inversion time inversion-recovery sequences. Images were analyzed quantitatively and qualitatively with regard to signal characteristics and pattern. MR findings were correlated with histopathologic findings. Wilcoxon signed rank test was used to compare results of signal-to-noise ratio calculations before and after USPIO administration. RESULTS: All knees with intraarticular injection of antigen suspension developed unilateral arthritis, whereas no signs of arthritis occurred in the control knees. On USPIO-enhanced images obtained 24 hours after contrast agent administration, significant T1 (P =.03) and more predominantly T2* (P =.02) and T2 effects (P =.01) were evident in the synovium of all 10 arthritic knees, which reflected USPIO uptake by macrophages in the synovial tissue. To a lesser extent, T2* effects were present also within the joint effusion (P =.01). No significant changes in signal characteristics were detected in the 10 nonarthritic knees in the antigen-injected group or the six knees in the control group (P =.06-.91). Histologic examination confirmed uptake of iron in the macrophages of arthritic knees. Changes in MR signal characteristics within the arthritic synovium and synovial effusion were visually detectable after intravenous administration of USPIO. CONCLUSION: MR imaging at 1.5 T can depict USPIO uptake in phagocytic-active macrophages in an antigen-induced arthritis animal model.     

Hepatocellular carcinoma in cirrhosis: enhancement patterns at dynamic gadolinium- and superparamagnetic iron oxide-enhanced T1-weighted MR imaging

PURPOSE: To prospectively compare intraindividual differences in enhancement patterns between gadolinium- and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging in patients with histologically proved hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty-two patients (18 men, four women; mean age, 58.9 years) with 36 pathologically proved HCC lesions underwent contrast material-enhanced dynamic T1-weighted gradient-echo MR imaging twice. Gadopentetate dimeglumine was used at the first session. After a mean interval of 5 days, a second session was performed with a bolus-injectable SPIO agent, ferucarbotran. Qualitative analysis of contrast enhancement patterns with each agent during hepatic arterial, portal venous, and equilibrium phases was performed by two readers who classified lesions as isointense, hypointense, or hyperintense compared with surrounding liver parenchyma and searched for presence of hyperintense peritumoral ring enhancement. Results of signal intensity analysis during different vascular phases at both sessions were compared by using the McNemar test, and kappa statistic was used to evaluate agreement between signal intensity and enhancement pattern of lesions during different vascular phases. RESULTS: On gadolinium-enhanced hepatic arterial phase images, HCC lesions (n = 36) were hyperintense in 21 (58%) cases, hypointense in 10 (28%), and isointense in five (14%). On ferucarbotran-enhanced hepatic arterial phase images, HCC lesions were isointense in 18 (50%) cases, hypointense in 11 (31%), and hyperintense in seven (19%). On gadolinium-enhanced portal venous and equilibrium phase images, respectively, HCC lesions were hypointense in 17 (47%) and 21 (58%) cases, hyperintense in 10 (28%) cases and one (3%) case, and isointense in nine (25%) and 14 (39%) cases. On ferucarbotran-enhanced portal venous and equilibrium phase images, respectively, HCC lesions were hypointense in 15 (42%) and 11 (31%) cases, hyperintense in three (8%) and three (8%) cases, and isointense in 18 (50%) and 22 (61%) cases. CONCLUSION: For HCC, contrast enhancement pattern on T1-weighted gradient-echo MR images shows marked variability with gadolinium or SPIO contrast agents.     

MR imaging detection of superparamagnetic iron oxide loaded tris-acryl embolization microspheres

PURPOSE: To assess by magnetic resonance (MR) imaging the detectability of superparamagnetic iron oxide (SPIO)-labeled microspheres (MSs) in vitro on gelose, ex vivo in kidneys from embolized sheep, and in vivo in kidneys from embolized pigs. MATERIALS AND METHODS: With various sizes of SPIO-labeled MSs, common neck and pelvic spin-echo and gradient-echo sequences were acquired on a 1.5-T MR unit. SPIO-labeled MSs of four sizes were embedded in a hydrogel as single MSs or in multiple units, or multiplets. Detection rate on MR imaging was assessed according to the real size and number of MSs. SPIO-loaded and unloaded MSs of four sizes were injected into eight sheep kidneys, which underwent MR and pathologic examinations. For each size, the location of MSs in renal vasculature was determined and compared according to the technique used. Kidneys were embolized in pigs with various amounts of MSs in three sizes. MR was performed immediately after embolization and SPIO-labeled MS detection was assessed according to size, organ, and amount injected. Results SPIO-labeled MSs provide a low signal intensity on T1-weighted sequences, without distortion. In vitro, 28% of 100-300-microm single MSs were detected and more than 80% were detected for larger sizes. MS multiplets were all detected in all sizes. Ex vivo, all sizes of MSs were detected by MR imaging in kidneys, whereas control MSs were not observed. Histologic analysis showed that there was no difference in vascular distribution between SPIO-labeled MS and control MSs, and therefore for each caliber (P > .05). Arterial location of SPIO-labeled MSs was the same on MR imaging and histologic analysis. In vivo, SPIO-labeled MS were detected in the kidney vasculature when volumes greater than 1 mL of 100-300-microm or 500-700-microm MSs were injected. Volumes lower than 1 mL SPIO-labeled MSs were hardly detected in kidneys, regardless of MS size. Conclusions SPIO-labeled MSs are detected by MR imaging with common gradient-echo sequences in vitro in gelose and ex vivo and in vivo in kidneys. SPIO-labeled MSs could allow better control of embolization and thereby enhance efficacy and safety of the procedure.