Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties,clinical development,and applications

Ferucarbotran (Resovist) is the second clinically approved superparamagnetic iron oxide developed for contrast-enhanced MRI of the liver. The purpose of this review is to provide an overview on the properties, clinical development, and application of ferucarbotran. Safety data obtained during clinical phases I–III revealed a total of 162 adverse events within 1053 patients, of which 75 were classified as possibly, probably, or definitely drug related. The majority of events occurred within the first 3 h (73 of 75) and was of mild intensity. The agent significantly improves the detection of hypovascular focal liver lesions with a comparable sensitivity in lesion detection to CTAP but without a relevant loss in specificity. Furthermore, ferucarbotran leads to a significant improvement of the sensitivity for lesion classification and characterization of the most frequent liver lesions. Contrast-enhanced MRA is not feasible and the angiographic effect is not sufficient to allow for postprocessing of data into maximum intensity projections. Intraindividual studies at low-field (0.2 T) and high-field (1.5 T) showed similar rates for lesion detection. The time window for contrast-enhanced MRI of the liver is at least 1 day up to 4 days. The compound can be regarded as safe and well tolerated. Even bolus injections caused no cardiovascular side effects, lumbar back pain, or clinically relevant laboratory changes. The examination time can be kept short with T1- and T2-weighted pre-contrast sequences, dynamic MRI over 10 min, and finally accumulation phase T2-weighted MRI. Patients who may benefit in particular are surgical candidates for resection, transplantation, or interventional therapies, and patients with liver cirrhosis and/or suspected hepatocellular carcinoma to either exclude malignancy or to define the extent of disease, the location of lesions, and the type of newly detected lesions. Electronic Publication     

Selective induction hyperthermia following transcatheter arterial embolization with a mixture of nano-sized magnetic particles (ferucarbotran) and embolic materials: feasibility study in rabbits

PURPOSE: To evaluate the possibility of selective hyperthermia following transcatheter arterial embolization (TAE) with ferucarbotran using a newly developed inductive heating (IH) device. MATERIALS AND METHODS: Twelve Japanese white rabbits were separated into four groups: those treated with TAE using a mixture of ferucarbotran and lipiodol (F-L group); those treated with ferucarbotran and gelatin sponge powder; those treated with saline and lipiodol; and a control group. These four groups received IH. Nine rabbits with renal VX2 carcinoma were separated into three groups: IH after TAE (IH-TAE tumor), TAE without IH (TAE tumor), and no treatment (control tumor). The temperature of the tumor was kept at 45 degrees C for 20 min. The therapeutic effect was pathologically evaluated by TUNEL staining. RESULTS: In the heating rates of the kidney, the F-L group showed significantly greater values than the group in which iron was not used. In the IH-TAE tumor group, tumors could be selectively heated. In TUNEL staining, the IH-TAE tumor and TAE tumor groups showed significantly greater values of apoptosis rate than in the control tumor group. CONCLUSION: IH following TAE with a mixture of ferucarbotran and lipiodol was capable of inducing selective hyperthermia with our device. However, further investigation is needed to confirm its safety and effectiveness in the treatment of malignant neoplasms in humans.     

The use of DWI to assess spleen and liver quantitative ADC changes in the detection of liver fibrosis stages in chronic viral hepatitis

This study aimed to evaluate the changes in spleen and liver diffusion-weighted magnetic resonance imaging (DWI) in chronic viral hepatitis patients.     

菲立磁增强MRI在肝脏局灶性病变诊断中的价值

目的 评价菲立磁增强MRI在肝脏实性占位性病变诊断中的应用价值。材料与方法 对21例怀疑有肝脏局灶性占位病变患者行MR平行及菲立磁增强MRI检查。扫描序列包括频率选择脂肪抑制及非脂肪抑制ASTE T2WI、True FISP T2WI、频率选择脂肪抑制FLASH T1WI。比较增强前后T2WI及T2WI病灶及肝脏的信噪比（SNR）及对比噪声比（CNR）;观察增强前后病灶数量及形态;结合MR平扫及增强MRI表现进行定性诊断。结果 菲立磁增强T2WI及T2WI肝脏信号强度较平扫明显下降,病灶与肝脏的CNR较平扫明显提高,差异具有统计学意义。结论 菲立磁增强T2WI及T2WI可明显提高肝脏实性占位性病灶的检出率。菲立磁增强T1WI在脏局灶性病变的定性诊断中具有潜在价值,有待于进一步开发与研究。     

菲立磁增强磁共振成像在肝脏疾病诊断中的价值

目的　评价菲立磁增强MRI在肝脏疾病诊断中的应用价值。方法　对 31例经CT或MRI检查确定或怀疑有肝脏病变者进一步行菲立磁增强MRI检查 ,分别测量增强前后肝脏、病变及背景噪声的T2 WI信号强度 ,计算增强前后肝脏及病变的信噪比(SNR)、对比噪声比 (CNR)。分析平扫及增强后扫描检测的病灶数目。结果　菲立磁增强后肝脏的SNR明显降低 (Ρ <0 .0 1) ;恶性病灶的SNR变化不明显 (Ρ >0 .0 5 ) ;病灶 -肝脏CNR明显增高 (Ρ <0 .0 1)。增强后病变的检出数量增加 ( χ2 =8.5 7,Ρ <0 .0 1)。结论　菲立磁能显著提高肝脏恶性肿瘤的检出率 ,而且对肝脏小病灶的鉴别诊断提供有利的依据     

核素脾显像观察7例严重脾外伤自体腹膜后带蒂移植脾功能

目的应用放射性核素脾显像评价严重脾外伤自体腹膜后脾移植的脾功能。方法对严重脾外伤患者行自体腹膜后带蒂脾移植术,应用99mTc-植酸钠胶体法和99mTc-热变性红细胞法观察自体脾移植后患者脾功能。结果术后2周、3个月及6个月分别观察到7例自体脾移植均成活,移植脾显像较清晰。结论99mTc-植酸钠和99mTc-热变性红细胞脾显像是直接观察严重脾外伤自体脾移植术后脾成活、功能和形态的有效方法。     

Resovist enhanced MR imaging of the liver: Does quantitative assessment help in focal lesion classification and characterization?

Purpose:

To improve characterization of focal liver lesions by a prospective quantitative analysis of percentage signal intensity change, in dynamic and late phases after slow (0.5 mL/s) Resovist administration.

Materials and Methods:

Seventy‐three patients were submitted on clinical indication to MR examination with Resovist. Signal intensity of 92 detected focal lesions (5–80 mm) were measured with regions of interest and normalized to paravertebral muscle in arterial, portal, equilibrium and T1/T2 late phases, by two observers in conference. Five values of percentage variations per patient were obtained and statistically evaluated.

Results:

The enhancement obtained on dynamic study is more suitable in hemangiomas and focal nodular hyperplasias than in adenomas and hepatocellular carcinomas. To discriminate benign versus malignant lesions on late‐phase‐T2‐weighted images, a cutoff = ?26%, allowed sensitivity and specificity values of 97.4% and 97.7%, respectively. Area under the receiver operating characteristic (ROC) curve was 0.99. To differentiate hemangioma versus all other focal liver lesions, on late‐phase‐T1‐weighted images, a cutoff = +40% permitted sensitivity and specificity values of 90.5% and 98.0%, respectively. Area under the ROC curve was 0.98.

Conclusion:

Late phase quantitative evaluation after slow Resovist administration, allows to differentiate malignant from benign hepatic masses and hemangiomas from all the others focal liver lesions, on T2‐/T1‐weighted acquisitions, respectively. J. Magn. Reson. Imaging 2009;30:1012–1020. © 2009 Wiley‐Liss, Inc.

     

Estimation of spleen volume using MR imaging and a random marking technique

The aim of this study was to apply a random marking volumetric technique in MR images for estimation of spleen volume. The MR imaging was performed in phantoms and 16 patients with indications unrelated to splenic disease. Images were transferred to a workstation to perform volumetric measurements using the random marking technique and the conventional technique of manual planimetry. Two observers independently measured splenic volume in order to evaluate reproducibility of both volumetric techniques. Phantom experiments revealed that the accuracy of the random marking technique and manual planimetry was approximately the same. In vivo splenic volume measurements derived from both volumetric techniques were highly correlated (r = 0.99, p < 0.0001). For both observers intraobserver variation was found to be lower with the random marking technique than with manual planimetry. Interobserver coefficient of variation using the manual planimetry was 4.6 % and was reduced to 2.9 % by adopting the random marking technique. The random marking technique was almost two times faster than the manual planimetry. The combination of the random marking technique with MR imaging might provide accurate, reproducible, quick splenic volume estimations. Received: 3 March 2000, Revised: 29 May 2000, Accepted: 30 May 2000     

超顺磁性氧化铁微粒对肝脏占位病变的诊断意义

目的：评价超顺磁性氧化铁（SPIO）对肝脏占位病变的显示及定性作用。材料和方法：30例肝脏占位性病 变,其中包括原发性肝癌（HCC）、胆管细胞化妆品 、转移性肝癌、局灶性结节增生、血管瘤及肝硬化结节。静脉注射SPIO后,用1.5T超导型MR扫描分别对病灶行10min、30min、45min、70min、和16h动态扫描。教育处肝实质和病灶的增强信噪比（CNR）和肝实质的相对强化比（RE）。并绘制其时间-信号强度曲线。结果：扫描结果显示在自旋回波和梯度回波的T2加权序列中,肝实质呈明显负性强化,肝内病灶中肝转移瘤信号强度无明显变化。HCC可呈轻度负性强化,肝血管瘤等良性病灶信号在扫描延迟可见轻度正性强化作用。结论：SPIO在T2加权中的负性强化作用对肝肿瘤的显示有良好的信噪比,对肝肿瘤的定性诊断是值得探讨的领域。     

MRI-findings of nodular lesions in an enlarged spleen, associated with visceral Leishmaniasis

We present a case of a 15-month-old Moroccan girl with fever of unknown origin, hepatosplenomegaly and multiple hypoechoic nodular splenic lesions that appear hypodense on CT. T2-weighted MRI sequences show a markedly inhomogeneous intensity of the parenchyma, seemingly caused by multiple ill-defined and heterogeneous hypointense nodules. Laboratory tests confirmed a recent infection with Leishmania, a parasite endemic to (sub)tropic regions. During and after therapy these lesions gradually resolved. To our knowledge this is the second published case in which different imaging modalities were able to demonstrate organ lesions associated with Leishmania. It is also the first report of MRI-findings associated with these lesions.     

Enhanced positive‐contrast visualization of paramagnetic contrast agents using phase images

Iron oxide–based MRI contrast agents are increasingly being used to noninvasively track cells, target molecular epitopes, and monitor gene expression in vivo. Detecting regions of contrast agent accumulation can be challenging if resulting contrast is subtle relative to endogenous tissue hypointensities. A postprocessing method is presented that yields enhanced positive‐contrast images from the phase map associated with T₂*‐weighted MRI data. As examples, the method was applied to an agarose gel phantom doped with superparamagnetic iron‐oxide nanoparticles and in vivo and ex vivo mouse brains inoculated with recombinant viruses delivering transgenes that induce overexpression of paramagnetic ferritin. Overall, this approach generates images that exhibit a 1‐ to 8‐fold improvement in contrast‐to‐noise ratio in regions where paramagnetic agents are present compared to conventional magnitude images. This approach can be used in conjunction with conventional T₂* pulse sequences, requires no prescans or increased scan time, and can be applied retrospectively to previously acquired data. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

正常成人脾脏大小的CT测量

目的:探讨CT测量正常成人脾脏大小的方法及其相关因素。方法:选择无引起脾脏增大因素的CT检查者241例。测量计算正常成人脾脏的体积、最大平面面积和脾门平面面积。对不同性别、年龄组的测量结果进行了比较分析。结果:122例男性和119例女性的脾脏体积分别为139.13±53.64 cm3和122.52±50.46 cm3(P=0.014);最大平面面积分别为27.74±8.22 cm2和25.08±6.75 cm2(P=0.007);脾门平面面积分别为25.67±8.12 cm2和23.34±6.55 cm2(P=0.015)。随着年龄的增大,脾脏的体积、最大平面面积和脾门平面面积均有缩小趋势,但各年龄组之间无显著性差异。脾脏的体积与最大平面面积、脾门平面面积之间的相关系数分别在0.839和0.758以上。结论:正常成人脾脏的体积与最大平面面积、脾门平面面积具有密切的相关性,后两者可用于临床评估脾脏的大小。脾脏大小与年龄、性别有一定的关系。     

14.1 T whole body MRI for detection of mesoangioblast stem cells in a murine model of Duchenne muscular dystrophy

Noninvasive imaging procedures will be important for stem cell therapy for muscular dystrophy (MD). Mesoangioblasts regenerate muscle in animal models of muscular dystrophy. In this study, superparamagnetic iron oxide nanoparticles were used to visualize mesoangioblasts in vivo with MRI. Mesoangioblasts incorporated superparamagnetic iron oxide without transfection reagents, and cell differentiation was not negatively impacted. A custom-built radiofrequency coil with an adjustable field of view and 14.1 T magnet were used for whole-body MRI of mice. High-resolution images of mesoangioblasts in skeletal and cardiac muscle of Mdx mice were obtained following local delivery. Labeled cells were verified by Prussian blue staining and dystrophin expression, indicating that the wild-type mesoangioblasts survived and differentiated in muscle. Iron-labeled cells were detected with MRI in vivo 6 months following intracardiac injection but were determined to be activated macrophages. Iron-labeled cells were not detected by MRI following systemic delivery but were present in skeletal and cardiac muscle, visualized by Prussian blue staining. Systemically delivered mesoangioblasts were detected in lungs by Prussian blue staining and DiI but not by MRI in our study. MRI may be useful for short-term tracking of mesoangioblasts delivered locally but not for long-term monitoring or detection after systemic delivery.     

Radiology of the spleen

The spleen is generally not considered a challenge to the radiologist. Most often it poses a problem by anomalies or an irregular but normal contrast enhancement; however, a variety of inflammatory, infectious and neoplastic diseases may involve the spleen. CT and ultrasonography are screening modalities for the spleen. For problem solving, MR imaging can be helpful, especially due to its free choice of the imaging plane and because of the high resolution in contrast MR imaging. Splenic angiography as a diagnostic tool has generally been replaced by CT, ultrasound, or MR and is now used as an interventional method, e. g., in non-surgical management of patients with chronic idiopathic thrombocytopenia or in patients with splenic trauma. This article reviews the radiology of the spleen, including anatomy, embryology, splenomegaly, splenic injury, infarction, cysts, tumors, abscesses, sarcoidosis, and AIDS. Knowledge about the use of different imaging modalities and underlying gross and microscopic pathologic features leads to a better understanding of the radiologic findings. Received: 4 November 1999 Revised: 12 May 2000 Accepted: 16 May 2000     

Cystic lymphangioma of the spleen: US-CT-MRI correlation

A case of a surgically confirmed cystic lymphangioma of the spleen is presented. Preoperative imaging consisted of US, contrast-enhanced CT and MRI, all showing a multiloculated lesion with small cystic cavities divided by thin septa, corresponding to dilated lymphatic spaces. Preoperative studies correlated well with the pathologic findings. Cystic lymphangioma of the spleen is a very rare condition and is usually solitary and asymptomatic. Large lymphangiomas may be an indication for splenectomy, since the risk of rupture is high even from minor abdominal trauma. Preoperative diagnosis may be achieved with correlated noninvasive imaging.     

Assessment of ablative margin after radiofrequency ablation for hepatocellular carcinoma; comparison between magnetic resonance imaging with ferucarbotran and enhanced CT with iodized oil deposition

Background and purpose

Our aim was to investigate whether magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation could accurately assess ablative margin when compared with enhanced computed tomography (CT) with iodized oil marking.

Materials and methods

We enrolled 27 patients with 32 hepatocellular carcinomas in which iodized oil deposits were visible throughout the nodule after transcatheter arterial chemoembolization. For these nodules, radiofrequency ablation was performed after ferucarbotran administration. We then performed T2-weighted MRI after 1 week and enhanced CT after 1 month. T2-weighted MRI demonstrated the ablative margin as a low-intensity rim. We classified the margin into three grades; margin (+): high-intensity area with a continuous low-intensity rim; margin zero: high-intensity area with a discontinuous low-intensity rim; and margin (−): high-intensity area extending beyond the low-intensity rim.

Results

In 28 (86%) of 32 nodules, there was agreement between MRI and CT. The overall agreement between for the two modalities in the assessment of ablative margin was good (κ = 0.759, 95% confidence interval: 0.480–1.000, p < 0.001). In four nodules, ablative margins on MRI were underestimated by one grade compared with CT.

Conclusion

MRI using ferucarbotran is less invasive and allows earlier assessment than CT. The MRI technique performed similarly to enhanced CT with iodized oil marking in evaluating the ablative margin after radiofrequency ablation.     

Superparamagnetic iron oxide (SPIO)-enhanced liver MRI with ferucarbotran: efficacy for characterization of focal liver lesions

PURPOSE: To evaluate the efficacy of ferucarbotran in T2-weighted (T2W) fast spin-echo (FSE) and T2*W gradient-echo (GRE) sequences for characterizing focal liver lesions. MATERIALS AND METHODS: In 68 patients, 46 malignant and 22 benign focal liver lesions were evaluated. Precontrast (NCE) T2W FSE images and contrast-enhanced (CE) T2W FSE and T2*W GRE images were obtained on a 1.5T MR system. Based on signal intensity (SI) measurements in focal lesions and liver parenchyma, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for all sequences. The percentage of SI loss (PSIL) in focal lesions after contrast agent (CA) application was calculated for the T2W FSE sequence. Qualitative analyses were performed to assess image quality and lesion conspicuity obtained with the CE-T2W FSE and CE-T2*W GRE sequences. RESULTS: The mean PSIL was higher in solid benign lesions than in malignant lesions (39.6% vs. 3.2%, P<0.05). With a threshold PSIL of 25%, the sensitivity and specificity for characterizing malignant lesions were 97.8% and 92.9%, respectively. The mean CNR of the malignant lesions was higher in the CE-T2*W sequence than in the CE- and NCE-T2W FSE sequences (29.9 vs. 22.7 (P<0.01) vs. 12.8 (P<0.01)). CE-T2*W images showed a superior image quality and lesion conspicuity (P<0.05) compared to the CE-T2W FSE sequence. CONCLUSION: The PSIL can be an accurate tool for characterizing benign and malignant lesions. The addition of a CE-T2*W GRE sequence is helpful for the detection and characterization of malignant lesions.     

Littoral cell angioma of the spleen: CT and MR imaging appearance

We report a case of littoral cell angioma (LCA) of the spleen, a recently described splenic pathology, which imaging characteristics and pathologic morphology have been discussed only by a few authors. The imaging findings in unenhanced and contrast-enhanced MRI and CT as well as histologic specimen are presented. Diagnosis was made after elective splenectomy. Differential diagnosis of splenic tumors as well as the imaging findings in this particular case are discussed. Received: 7 July 1999; Revised: 18 January 2000; Accepted: 19 January 2000     

部份性脾栓塞术后并发急性胰腺炎的探讨(附7例报告)

于1990-05～1994-05间,采用部份性脾栓塞术治疗各种血液病共52例,其中7例术后并发急性胰腺炎,发生率13.5%.作者对PSE术后并发急性胰腺炎的机理进行了探讨,认为其发生与3个重要因素有关:(1)部分胰腺动脉分支被栓塞;(2)造影剂大量灌注引起胰腺微循环量和血液成份的改变;(3)离子型造影剂的毒性作用.