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.     

MRI in focal liver disease: A comparison of small and ultra-small superparamagnetic iron oxide as hepatic contrast agents

The purpose of this study was to compare small and ultrasmall superparamagnetic iron oxide particles (SPIO and USPIO, respectively) as MR contrast agents for the evaluation of focal hepatic disease. In two different patient groups (SPIO [n = 53], USPIO [n = 27]), with focal liver disease (metastases, hepatocellular carcinoma [HCC], hepatocellular adenoma [HCA], and focal nodular hyperplasia [FNH]), spin-echo T1- and T2-weighted images (T1WI, T2WI) were obtained at 1.0T, before and after intravenous contrast administration. The percentage signal-to-noise ratio (SNR) change and lesion-to-liver contrast (LLC) were measured and statistically compared. The liver decreased in signal intensity (SI) after SPIO administration (?28%) and increased after USPIO administration (+16%) on T1WI. On T2WI, the liver decreased in SI on postcontrast images with both agents (?78% SPIO, ?73% USPIO). This difference was not statistically significantly different (P ? .07). Both SPIO and USPIO provided >500% improvement in LLC on T2WI. On T1WI, LLC was increased in metastases (120%) and HCC (325%) with SPIO. Post-USPIO, LLC was increased on T1WI only in metastases (>500%). Both SPIO and USPIO show excellent hepatic uptake, presumed secondary to reticuloendothelial activity, based on the degree of %SI change seen in the liver after administration of contrast on T2WI. However, USPIO preparations exhibit blood pool activity that may aid in further characterization of focal liver lesions, as is evidenced by their greater T1 effect in the liver and in some focal liver lesions.     

Improved focal liver lesion detection: comparison of single-shot spin-echo echo-planar and superparamagnetic iron oxide (SPIO)-enhanced MRI

PURPOSE: To prospectively compare single-shot spin-echo echo-planar imaging (SSSE-EPI) using b = 0, 10, 150, and 400 seconds/mm(2) with standard MRI techniques after intravenous super paramagnetic iron oxide (SPIO) in the detection and characterization of focal liver lesions with focus on small (<10 mm) focal liver lesions. MATERIALS AND METHODS: A total of 25 patients suspected for colorectal liver metastases were included. Number of detected lesions was evaluated. Image quality was compared between SSSE-EPI sequence and post-SPIO (fat-suppressed T1-weighted [T1w] gradient echo [GE], T2-weighted [T2w] turbo spin echo [TSE] and T2* GE) sequences using rank order statistic (RIDIT). Lesion characterization was performed for SSSE-EPI and for all remaining sequences pre- and post-SPIO. Reference standard comprised surgery, biopsy, and/or follow-up. RESULTS: Reference standard demonstrated 25 hemangiomas and 70 metastases. Best lesion detection respectively best image quality (P < 0.05) was achieved with SSSE-EPI (b = 10 seconds/mm(2)) post-SPIO T1w GE and T2w turbo spin echo. Lesion characterization using all sequences pre- and post-SPIO performed best for lesion characterization compared with SSSE-EPI. CONCLUSION: This preliminary study shows the potential of SSSE-EPI as a stand-alone sequence for the detection of liver hemangiomas and metastases when compared with SPIO-enhanced imaging. Sequences pre- and post-SPIO are needed for qualitative lesion characterization.     

肝脏局灶性病变MR动态增强扫描及临床意义

目的探讨肝脏局灶性病变ＭＲ动态增强扫描方法及临床意义。方法作者前瞻性研究了１３６例肝脏局灶性病变，包括肝细胞性肝癌、周围型肝内胆管细胞性肝癌、转移瘤及海绵状血管瘤。采用平静呼吸状态下梯度回波Ｋ空间中心部分采集技术、７个连续层面８个时相动态增强扫描。结果各例均动态增强扫描成功。动态扫描显示时间信号强度曲线在肝细胞性肝癌呈速升速降型；胆管细胞癌呈渐升型；转移瘤呈环形强化，缓慢升高型；海绵状血管瘤呈速升平台型。结论平静呼吸下Ｋ空间中心部分采集肝脏动态扫描，可以显示肝脏局灶病变的血供状态，而且不同病变具有不同的强化特征。     

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。     

肝脏局灶性病变MRI表现与病理学的相关性研究

肝脏局灶性病变的MRI信号强度受许多病理因素的影响。病变的组织学特征:细胞构成、血液供应、间质构成和肿瘤内的坏死或者出血等,都会使病变的T1及T2弛豫时间发生显著变化。细胞内的某些内容物:糖原、脂肪、黑色素、铁和铜,在决定MRI信号表现方面起着重要的作用。MRI与病理学之间联系的研究对于诊断局灶性病变非常有帮助。     

Sequential use of ferumoxide particles and gadolinium chelate for the evaluation of focal liver lesions on MRI

This study describes the sequential use of ferumoxide (superparamagnetic iron oxide) particles and nonspecific extracellular gadolinium chelate (Gd) for evaluation of focal liver lesions on MRI to evaluate order of contrast administration and imaging effect of the first contrast agent on sequences acquired after the second contrast agent. Thirteen patients underwent MR examinations that included ferumoxide and Gd. The order and timing of administration were as follows: separate sessions (three patients; Gd study 4-19 days before ferumoxide study), same session, Gd first (seven patients; Gd study 1-2 hours before ferumoxide study), and same session, ferumoxide first (three patients; ferumoxide administered less than 1 hour before Gd study). Postcontrast sequences were reviewed in a randomized, blinded fashion by two separate investigators. Determination was made regarding whether (a) the presence of the first agent administered could be detected on sequences obtained after the second agent and (b) the presence of the first agent interfered with the image quality of those sequences. No evidence for the presence of Gd was appreciated by either observer on postferumoxide sequences acquired in separate session studies. In same session, Gd first studies, the presence of Gd was observed in six of seven patients on T1-weighted spoiled gradient-echo (SGE) images obtained after ferumoxide administration. The presence of Gd was not apparent in seven of seven patients on T2-weighted fat-suppressed images obtained after ferumoxide. In same session, ferumoxide first studies, the presence of ferumoxide was appreciated on post-Gd sequences in two of three patients. The presence of ferumoxide did not appreciably diminish image quality on those sequences. Exact agreement was achieved by the independent investigators. Our results suggest that Gd and ferumoxide can be administered sequentially within one study session without substantial loss of diagnostic information obtained on sequences performed after administration of the second contrast agent. Administrating Gd first resulted in less of an effect of the visualization of the first agent on sequences acquired after the second agent.     

MRI in characterization of focal liver lesions: Comparison of T2 weighting by conventional spin-echo and turbo spin-echo sequences

Forty-one patients with 61 proved focal liver lesions underwent MRI of the liver at 1.0 T, with the aim of evaluating the usefulness of turbo spin-echo (TSE) sequences in characterizing focal liver lesions, by comparing them with conventional spin-echo (CSE) sequences. Two different TSE protocols were employed, with constant echo time and varying repetition time: TSE-S (3000 msec) and TSE-L (5100 msec). All images were evaluated quantitatively (signal-to-noise ratio ‘SNR’) and qualitatively: because benign lesions were all liquid (12 cysts and 10 hemangiomas), they were well characterized morphologically on the basis of signal intensity. Mean SNR was significantly different between metastases and benign lesions (P < .0001) with all T2 sequences. Among the single T2 sequences tested, logistic regression analysis showed TSE-L to have the best predictive ability of the nature of focal lesions, with a G value of 42.02, compared to 29.87 of TSE-S and 25.55 of CSE second echo (SE II). The combination of TSE-L with TSE-S did not modify these results, whereas the combination of TSE-L with CSE only resulted in slight improvement (G = 46.95). Comparison of the receiver operating characteristic (ROC) curves showed only SE II (area under the ROC curve of .8312) to be significantly inferior to the best single sequence, or TSE-L (area under the ROC curve of .9176; P = .027). All sequences were equivalent in qualitative evaluation, with good reproducibility, sensitivity ranging from .94 to 1.0, and specificity ranging from .86 to .93. This study confirms the value of TSE sequences in characterization of focal liver lesions. Time of acquisition is strongly reduced with these sequences, whereas results are fairly similar to those obtained with CSE. TSE sequences could therefore replace CSE for the study of focal liver lesions.     

Detection and characterization of benign focal liver lesions with multislice CT

MDCT is a rapidly evolving technique that significantly improves CT imaging for several indications including depiction of focal benign lesions. Imaging mainly profits from improved longitudinal spatial resolution allowing high-quality non-axial reformations and 3D reconstructions and CT angiography as well as rapid accurate multiphase imaging with short breath-holding periods. This review provides an overview of the current status of MDCT with respect to liver imaging and the implications for characterizing benign focal liver lesions. MDCT currently allows the acquisition of thin slices in daily routine diagnostics providing an improved detection rate of small liver lesions. Whereas large benign focal liver lesions exhibit typical patterns of morphology, attenuation and perfusion, which also may be assessed with single-slice scanners, small lesions remain challenging even with MDCT, since the specific criteria for confident diagnosis become more ambiguous. Here, MR imaging provides more detailed information about tissue components and the availability of liver-specific contrast agents, adding further impact to this technique. With respect to dose considerations, the number of necessary multiphase scans as well as the application of very thin collimation should be strictly checked for each patient undergoing MDCT based on the individual clinical situation and question.     

The influence of MR field strength on the detection of focal liver lesions with superparamagnetic iron oxide

The purpose of this study was to compare the value of low- vs high-field MR systems in the detection of focal liver lesions after IV administration of iron oxide particles. A prospective study was undertaken which included 20 patients with focal liver lesions on CT or US, or strong clinical suspicion of focal liver disease. Iron oxide particles were administered in an IV drip infusion over 30 min. Magnetic resonance imaging was subsequently performed on a 0.2 and a 1.5-T system. Both examinations were performed in one session. Turbo spin-echo T2-weighted sequences were used for further analysis (at 0.2 T: TR 4050 ms, TE 96 ms; 1.5 T: TR 3000 ms, TE 103 ms). After randomisation, images were analysed by two blinded readers. The evaluation included lesion counts, determination of lesion conspicuity and overall image quality (both graded on a scale 1–5). Quantitative analysis was performed on 29 lesions. Lesion-to-liver signal intensity and contrast-to-noise ratios (CNRs) were calculated. The total lesion count (cumulative counts for two observers) was 59 on the high-field system and 63 on the low-field system. Statistical analysis showed no significant difference. On both systems median value for lesion conspicuity was 3. No statistically significant difference was found. Global image quality was rated higher on the high-field system: 3 vs 2 for the low-field system (p = 0.0017). Quantitative analysis showed no significant difference for lesion-to-liver signal intensity ratios or CNRs. Although subjective image quality is significantly better on the high-field system, this does not result in better lesion detection or better lesion conspicuity. No significant difference in objective quantitative parameters was found in our series. Received 25 June 1996; Revision received 28 October 1996; Accepted 25 November 1996     

Ultrasound of focal liver lesions

This paper gives a comprehensive overview of ultrasound of focal liver lesions. Technical aspects such as examination technique and the use of Doppler modes as well as recent developments such as tissue harmonic imaging and microbubble contrast agents are discussed. The clinical significance and sonographic features of various liver lesions such as haemangioma, focal nodular hyperplasia, adenoma, regenerative nodule, metastasis, hepatocellular carcinoma and various types of focal infections are described. With the exception of cysts and typical haemangiomas, definitive characterisation of a liver lesion is often not possible on conventional ultrasound. This situation has changed with the recent advent of ultrasound contrast agents, which permit definitive diagnosis of most lesions. Contrast-enhanced sonography using recently developed contrast-specific imaging modes dramatically extends the role of liver ultrasound by improving its specificity in the detection and characterisation of focal lesions to rival CT and MRI.     

Gadobenate dimeglumine-enhanced liver MR imaging: value of dynamic and delayed imaging for the characterization and detection of focal liver lesions

The aim of this study was to determine the value of delayed-phase imaging (DPI) of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging for the evaluation of focal hepatic tumors compared with precontrast imaging and early dynamic phase imaging. The MR images were obtained in 48 patients with 98 focal hepatic tumors. Three-dimensional gradient-echo (GRE) imaging obtained before and 30, 60, and 1 h after administration of 0.1 mmol/kg of gadobenate dimeglumine. Each image set was analyzed qualitatively (lesion detection, conspicuity, delineation, and enhancement pattern on DPI) and quantitatively [signal-to-noise ratio (SNR), tumor–liver contrast-to-noise ratio (CNR)]. Improved lesion-to-liver contrast during the dynamic phase imaging was observed compared with precontrast images. The DPI showed a homogeneous enhancement of liver parenchyma and distinctive enhancement features of focal liver lesions: metastases (85%) showed a target shaped enhancement, and hepatocellular carcinomas (HCCs) showed an inhomogeneous (58%) or homogeneous enhancement (21%). The DPI showed better performance for the detection of metastases than other images by increasing lesion delineation (p<0.05). The absolute CNR of metastasis measured from periphery of the tumors on DPI was greater than precontrast and arterial phase imaging (p<0.05). The Gd-BOPTA during both dynamic and delayed phases provides valuable information for the characterization of focal liver lesions, and furthermore, Gd-BOPTA-enhanced DPI contributed to the improved detection of liver metastasis compared to precontrast and early dynamic imaging.     

Diffusion-weighted MRI in a liver protocol: its role in focal lesion detection

AIM: To evaluate the role of diffusion-weighted imaging (DWI) in the detection of focal liver lesions (FLLs), using a conventional magnetic resonance imaging (MRI) protocol. METHODS: Fifty-two patients (22 males, average age 55.6 years, range: 25-82 years), studied using a 1.5 Tesla magnetic resonance scanner, were retrospectively analyzed; detection of FLLs was evaluated by considering the number of lesions observed with the following sequences: (1) respiratory-triggered diffusion-weighted single-shot echo-planar (DW SS-EP) sequences; (2) fat-suppressed fast spin-echo (fs-FSE) T2 weighted sequences; (3) steady-state free precession (SSFP) images; and (4) dynamic triphasic gadolinium-enhanced images, acquired with three-dimensional fast spoiled gradient-echo (3D FSPGR). Two radiologists independently reviewed the images: they were blinded to their respective reports. DW SS-EP sequences were compared to fs-FSE, SSFP and dynamic gadolinium-enhanced acquisitions using a t -test. Pairs were compared for the detection of: (1) all FLLs; (2) benign FLLs; (3) malignant FLLs; (4) metastases; and (5) hepatocellular carcinoma (HCC). RESULTS: Interobserver agreement was very good (weighted = 0.926, CI = 0.880-0.971); on the consensus reading, 277 FLLs were detected. In the comparison with fs-FSE, DW SS-EP sequences had a significantly higher score in the detection of all FLLs, benign FLLs, malignant FLLs and metastases; no statistical difference was observed in the detection of hepatocellular carcinoma (HCCs). In the comparison with SSFP sequences, DW SS-EP had significantly higher scores (P < 0.05) in the detection of all lesions, benign lesions, malignant lesions, metastases and HCC. All FLLs were better detected by dynamic 3D FSGR enhanced acquisition, with P = 0.0023 for reader 1 and P = 0.0086 for reader 2 in the comparison with DW SS-EP sequences; with reference to benign FLLs, DW SS-EP showed lower values than 3D FSPGR enhanced acquisition (P < 0.05). No statistical differences were observed in the detection of malignant lesions and metastases; considering HCCs, a very slight difference was reported by reader 1 (P = 0.049), whereas no difference was found by reader 2 (P = 0.06). CONCLUSION: In lesion detection, DWI had higher scores than T2 sequences; considering malignant FLLs, no statistical difference was observed between DWI and dynamic gadolinium images.     

Superparamagnetic iron oxide: Detection of focal liver lesions at high-field-strength MR imaging

AMI-25 was evaluated at 1.5 T as a superparamagnetic iron oxide contrast agent for the liver. Sixteen patients with up to five suspected focal liver lesions were examined with T1-, proton-density—, and T2-weighted spin-echo sequences before and after intravenous administration of AMI-25 (15 μmol/kg iron). The contrast-to-noise ratio (C/N) increased from 1.8 to 3.5 on 600/15 (TR msec/TE msec) images and from 1.7 to 7.9 on 2,500/15 images after AMI-25 administration (P <.01). C/N did not change significantly on 2,500/90 images. Two blinded readers counted the number of lesions visible on unenhanced and contrast-enhanced images, with the 32 sets of images of the 16 patients presented in random order. Both readers identified more lesions on AMI-25–enhanced images, but the difference was not statistically significant (P >.05). Two patients reported minor side effects (flushing, sensation of heat, lower back pain). On the basis of the results obtained in a limited number of patients, the authors conclude that at 1.5 T, AMI-25 does not significantly improve the detection of focal liver lesions on conventional spin-echo images.     

扩散加权MRI定性诊断肝脏局灶性病变的研究

目的探讨MR扩散加权成像(DWI)对肝脏局灶性病变定性诊断的价值。方法对70例肝脏局灶性病变行DWI,计测表观扩散系数(ADC)值,同时作多期动态增强MRI,观察病灶各期强化模式。结果肝细胞癌、胆管细胞癌及转移癌的ADC值(单位mm2·s-1·10-3)分别为133±017、123±017、129±013,三者之间差异无统计学意义(P>005);肝血管瘤、肝囊肿ADC值分别为233±022、404±051,恶性肿瘤ADC值均低于良性病变。恶性肿瘤平均ADC值129±016;与良性病变间差异有统计学意义(P<005)。在动态增强扫描中,371%肝癌、789%胆管细胞癌与319%转移瘤病灶可见门静脉期与延迟期强化。结论DWI可成为1种有用的定性诊断肝脏局灶性病变的方法。     

Benign focal liver lesions: spectrum of findings on SonoVue-enhanced pulse-inversion ultrasonography

The prevalence of benign focal liver lesions (BFLL) is high both in the general population and in patients with known malignancies. The gray-scale ultrasound (US) technique is usually the first-line imaging modality used in the radiological workup of such lesions, but unfortunately it lacks specificity. Furthermore, Doppler examination may often be unsatisfactory owing to motion artefacts, or when small or deeply located lesions are evaluated. Recently, microbubble-based contrast agents used in combination with gray-scale US techniques, which are very sensitive to nonlinear behavior of microbubbles, have led to a better depiction of both microvasculature and macrovasculature of focal hepatic masses, thus improving the reliability of using US in the assessment of liver tumors. This review illustrates the spectrum of enhancement patterns of BFLL on contrast-enhanced ultrasonography with SonoVue, a second-generation microbubble-based contrast agent.This paper is based on a work accepted for presentation as a scientific paper at the Scientific Assembly and Annual Meeting of the ECR 2004.     

The role of SPIO-enhanced MRI in the detection of malignant liver lesions

The aim of this study was to evaluate the efficacy of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the detection of malignant liver tumors. MRI, using fast spin-echo T₂-weighted and gradient-echo T₁-weighted imagings before and after SPIO infusion, was performed in 32 patients with known or suspected hepatic lesions. Statistical analysis was performed using lesion-by-lesion analysis. SPIO-enhanced T₂-weighted MRI showed results comparable to those of unenhanced T₂-weighted MRI in the detection of focal liver lesions.     

Non-invasive liver iron concentration measurement by MRI: comparison of two validated protocols

In the non-invasive determination of the liver iron concentration several validated MRI methods are available, two of which are compared in this study. Twenty-eight patients were examined by MRI and evaluated by the methods of Kreeftenberg et al. [Kreeftenberg Jr HG, Mooyaart EL, Huizenga JR, Sluiter WJ, Kreeftenberg Sr HG. Quantification of liver iron concentration with magnetic resonance imaging by combining T1-, T2-weighted spin echo sequences and a gradient echo sequence. Neth J Med 2000;56:133-7] and Gandon et al. [Gandon Y, Olivie D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357-62]. It is concluded that the latter shows a better inter- and intra-observer correlation and is more accurate because of the automated preselection of one of five sequences most sensitive in the estimated liver iron concentration range. In the Kreeftenberg method combining the results of three suboptimal sequences, leads to underestimation of the liver iron concentration.     

Limits of detection of SPIO at 3.0 T using T2 relaxometry.

T(2)* relaxometry for quantitative MR imaging is strongly hampered by large-scale field inhomogeneities, which lead to signal losses and an overestimation of the relaxation rate R(2)*. This is of particular importance for the sensitive detection of iron oxide contrast agent distributions. To derive an accurate measurement of T(2)*, a main field inhomogeneity correction is applied: the main field inhomogeneity is derived from multislice T(2)* relaxometry data and used as an initial value for an iterative optimization, by which the relaxation signal is corrected for each voxel. These corrected T(2)* maps show reduced influence of the local field variation and contain information about the local SPIO concentration. The method was tested on phantoms and the limit of detection of SPIO labeled cells using T(2)* relaxometry was estimated in volunteers to be 120 x 10(3) cells/mL (2.4 microg Fe/mL) in the brain and 385 x 10(3) cells/mL (8 microg Fe/mL) in the liver.