Contrast-enhanced MR imaging of the liver: Comparison between Gd-BOPTA and mangafodipir

The purpose of the study was to evaluate the MR contrast agents gadolinium benzyloxypropionictetro-acetate (Gd-BOPTA) and Mangafodipir for liver enhancement and the lesion-liver contrast on T1W spin-echo (SE) and gradient-recalled-echo (GRE) images. Fifty-one patients (three groups of 17 patients each) with known or suspected liver lesions were evaluated with T1W SE (300/12) and GRE (77-80/2.3-2.5/80°) images before and after intravenous (IV) Gd-BOPTA (0.1 or 0.05 mmol/kg) or Mangafodipir (5 μmol/kg) in phase II to III clinical trials. Quantitative analysis by calculating liver signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and spleen-liver CNR was performed. Liver SNR and spleen-liver CNR were always significantly increased postcontrast. SNR was highest after application of 0.1 mmol/kg Gd-BOPTA (51.3 ± 3.6, P < .05). CNR was highest after Mangafodipir (?22.6 ± 2.7), but this was not significantly different from others (P = .07). Overall, GRE images were superior to SE images for SNR and CNR. Mangafodipir and Gd-BOPTA (0.1 mmol/kg) provide equal liver enhancement and lesion conspicuity postcontrast. By all criteria, contrast-enhanced T1-weighted GRE were comparable to SE images.     

Multifocal inflammatory pseudotumor of the liver: dynamic gadolinium-enhanced, ferumoxides-enhanced, and mangafodipir trisodium-enhanced MR imaging findings

The MRI characteristics of a multifocal inflammatory pseudotumor of the liver are described. Emphasis is placed on the appearances following intravenous administration of both non-specific and liver-specific MR contrast agents. On post-gadolinium gradient-echo (GE) images an early, intense, and peripheral enhancement was followed by a homogeneous, complete, and persistent enhancement. Lesions showed no uptake following administration of ferumoxides particles nor mangafodipir trisodium, respectively. During follow-up, a peripheral hyperintense rim appeared on precontrast T1-weighted images, a feature not previously described.     

False-negative MR imaging of malignant breast tumors

In this study we analyze MR-negative malignant lesions of the breast. A total of 204 patients with palpable and/or mammographic lesions were studied. The MR technique consisted of the turbo FLASH and MP-RAGE subtraction techniques. All patients underwent surgical biopsy and/or mastectomy and all specimens were examined by the correlative radiologic-histologic mapping technique. A total of 208 lesions were evaluated; 145 turned out to be malignant and 63 proved to be benign. Six malignant lesions were misinterpreted as benign on MR imaging; thus, suspicious contrast enhancement was present in 96 % of the lesions detected by mammography, US, or clinical examination. Especially 4 of the 17 ductal carcinoma in situ (DCIS) lesions were misinterpreted (23.5 %). Despite optimal technique, 6 malignant lesions were not identified by MR imaging. The highest prevalence of these MR occult lesions was in the group of DCIS. Although MR imaging has an important role in the evaluation of breast lesions and, primarily, in ruling out malignancy, one should be aware of the fact that false-negative MR findings do occur. Received 8 July 1996; Revision received 7 October 1996; Accepted 6 February 1997     

Contrast enhancement with GD-EOB-DTPA in MR imaging of hepatocellular carcinoma in mice: A comparison with superparamagnetic iron oxide

The purpose of this study was to evaluate the ability of the new liver-specific magnetic resonance contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) to detect hepatocellular carcinoma (HCC). Seventeen mice with 66 chemically induced HCCs underwent magnetic resonance imaging with both Gd-EOB-DTPA (30 μmol/kg) and superparamagnetic iron oxide (SPIO; 10 μmol/kg). After enhancement, lesion-to-liver contrast-to-noise ratios (CNRs) of 47 detected HCCs increased negatively from 3.7 ± 10.7 (mean ± SD) to –55.1 ± 25.8 with Gd-EOB-DTPA (P < .001) and increased positively from 10.4 ± 10.4 to 26.1 ± 16.3 with SPIO (P < .001). The improvement of CNR after administration of SPIO was less in smaller lesions (< 4 mm), whereas that after administration of Gd-EOB-DTPA was independent of lesion size. However, Gd-EOB-DTPA positively enhanced four HCCs (8.5%), both highly differentiated (grade 1) and moderately differentiated (grade 2). Gd-EOB-DTPA allows the conspicuous detection of small HCCs; however, moderately differentiated HCCs occasionally may be positively enhanced.     

Mn-DPDP–enhanced MR imaging of malignant liver lesions: Efficacy and safety in 20 patients

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 μmol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 μmol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occured at the 50 μmol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 μmol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%–137.5%) than the 50 μmol/mL formulation (46.2%–86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP–enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 μmol/kg Mn-DPDP at a concentration of 10 μmol/mL is safe and efficient enough to proceed to further clinical trials.     

The pseudocapsule in hepatocellular carcinoma: correlation between dynamic MR imaging and pathology

Nodular hepatocellular carcinoma (HCC) is characterized by the presence of a pseudocapsule (constructed usually from connective fibrous tissue) that appears hypointense on T1- and T2-weighted spin-echo (SE) and gradient-echo (GE) MR imaging sequences without a contrast medium. The presence of vascular structures inside the tumor, which are verified by histological exam, affects enhancement of the PC after administrating the contrast medium: The impregnation is more evident in the dynamic study but also persists on the delayed T1-weighted SE images. The accuracy of MR in detecting the pseudocapsule of HCC and contrast enhancement of the pseudocapsule during dynamic studies were evaluated and related to pathological findings. Thirty-seven HCC were examined in 33 patients and afterwards resected. In capsulated nodules, besides usual hematoxylin, eosin, and trichrome stainings, histochemical and immunohistochemical methods were performed. On a 1.5-T MR unit, T1- and T2-weighted SE and GE FLASH 2D sequences after intravenous injection of Gd-DTPA (dynamic study) were used. In a later phase, T1-weighted SE sequences were repeated. Histologically, the pseudocapsule (thickness 0.2–6 mm) was present in 26 of 37 nodules (70 %). The dynamic study was the most suitable technique to show the pseudocapsule, which was recognized in 80.7 % (21 of 26 nodules). In 5 of 26 cases, the pseudocapsule, not demonstrated by MR, was thinner than 0.4 mm. In 16 of 21 cases, in the early portal phase (30–60 s), the pseudocapsule had an early enhancement, which was more evident later; in 5 of 21 cases the enhancement was observed only in the late portal phase (1–2 min). At histological examination, 14 of 16 pseudocapsules with early enhancement showed a more prominent vasculature than those with enhancement in the equilibrium phase. Magnetic resonance was a reliable tool in demonstrating the pseudocapsule of HCC. The histological examination demonstrated a good correlation between the enhancement behavior and the vessel number of the pseudocapsule. Received: 28 July 1997; Revision received: 9 February 1998; Accepted: 20 March 1998     

Effect of field strength on gadolinium enhancement in MR imaging

This studv was designed to evaluate the influence of magnetic field strength on the relative enhancement effect (RE) of gadolinium (Gd)-chelates. Dilution series of two paramagnetic contrast agents (Gd-DTPA and Gd-DOTA) were examined in three commercially available MR systems. operating at different field strengths (02 T, 1. T, and 1.5 T). The RE was plotted against Gd concentration. The highest increases in signal intensity occurred with Gd concentrations of approximately L.0 mmol/L. No significant difference in RE was observed between MR systems ranging in field strength from 0.? T to 1.5 T. The RE of Gd-DTPA and Gd-DOTA was found to he equivalent.     

Hepatocellular carcinoma exhibiting a concentric structure of different histologic grades: Evaluation by chondroitin sulfate iron colloid-enhanced MR imaging

A patient with hepatocellular carcinoma exhibiting a concentric structure of different histologic grades was examined with chondroitin sulfate iron colloid (CSIC)-enhanced MR imaging. After CSIC injection, the advanced component was enhanced in comparison with the surrounding liver, and the well-differentiated component was not enhanced. CSIC-enhanced MR imaging was helpful in evaluating histologic grade on the basis of reticuloendothelial function.     

Direct hepatic tumor injection in rats: Can it be used for analysis of MR imaging contrast agents?

With a recently described rat model technique for direct hepatic injection of tumor cells for imaging research, there were concerns that the injection itself might produce lesions detectable with magnetic resonance (MR) imaging, thereby producing false-positive results. To examine this possibility, the authors prospectively studied 14 Sprague-Dawley rats after direct hepatic injection of cells from a rat hepatoma cell line. The rats were imaged with a variety of pulse sequences before and after intravenous injection of the contrast agent manganese dipyridoxal diphosphate at a dose of 8 mumol/kg. No intrahepatic lesions could be detected with MR imaging during the first 6 days after direct hepatic injection of the tumor cells. Therefore, the direct injection technique should be accurate for evaluating various MR imaging sequences and contrast agents for early hepatic tumor detection.     

Dynamic gadolinium-enhanced echo-planar MR imaging of the liver: Effect of pulse sequence and dose on enhancement

To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine—enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1, 0.2, and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine—enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine—enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization.     

Focal nodular hyperplasia of the liver on ferumoxides-enhanced MR imaging: features on conventional spin-echo, fast spin-echo and gradient-echo pulse sequences

The aim of this study was to assess the efficacy of a superparamagnetic iron oxide, ferumoxides, in the detection and characterization of focal nodular hyperplasia (FNH) on MR conventional spin-echo (SE), fast spin-echo (FSE) and gradient-echo (GRE) images. Fourteen adults with 27 FNHs were evaluated at 1.5 T before and after injection of ferumoxides. T1-weighted and T2-weighted SE, T2-weighted FSE and T2^*-weighted GRE sequences were used and analysed qualitatively and quantitatively. One hundred percent of FNHs showed a significant postcontrast decrease in signal intensity on T2- and T2*-weighted images. Heavily T2-weighted SE images showed the maximum decrease in FNH signal-to-noise ratio (S/N). Postcontrast GRE T2^*-weighted images improved the detection of the central scar and the delineation of FNHs and demonstrated the best lesion-to-liver contrast-to-noise ratio (C/N). Postcontrast T1-weighted SE images showed the least lesion-to-liver C/N. Ferumoxides-enhanced MR imaging can help detect and characterize FNH. Conventional pre- and postcontrast T2-weighted SE images and postcontrast GRE T2*-weighted images should be used preferentially. Received: 30 November 1998; Revised: 5 April 1999; Accepted: 6 April 1999     

Comparison of three different injection methods for arterial phase of Gd-EOB-DTPA enhanced MR imaging of the liver

Objective

To compare three different injection methods for optimizing hepatic arterial phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) enhanced MR imaging.

Methods

Arterial phase images were obtained after the injection of contrast agent at a rate of 3 mL/s with diluted Gd-EOB-DTPA (dilution method) in 27 patients, 3 mL/s with undiluted Gd-EOB-DTPA (3 mL method) in 26 patients and 1 mL/s with undiluted Gd-EOB-DTPA (1 mL method) in 28 patients. In the quantitative evaluation, signal-to-phantom ratios (SPR) of the liver parenchyma, pancreas, renal cortex, portal vein and aorta were evaluated. In the qualitative evaluation, the seven items for image quality of hepatic arterial phase were assessed, and the total score of all items in each subject was calculated.

Results

The score of enhancement of abdominal aorta and total score of seven items in 1 mL method were significantly higher than those in 3 mL method. The SPR of the liver parenchyma in 3 mL method was significantly higher than that in 1 mL method, suggesting substantial hepatic inflow from portal venous return.

Conclusion

For the optimal arterial phase imaging, injection rate of 1 mL/s with undiluted Gd-EOB-DTPA is convenient and preferable, compared with other two methods, based on our qualitative analysis.     

Hepatic tumors: Magnetization transfer MR imaging with gadolinium enhancement

Thirty patients with 15 hepatocellular carcinomas, 10 metastases, four hemangiomas, and one cholangiocarcinoma underwent magnetic resonance imaging at 1.5 T with T1-weighted, T2- weighted spin-echo (SE) images, gradient-echo (GRE) magnetization transfer (MT) images, and gadolinium-enhanced T1-weighted SE and MT- GRE images. The MT effect and lesion-liver contrast-to-noise ratio (C/N) were calculated and visual assessment (qualitative analysis) performed for unenhanced and enhanced MT-GRE images and enhanced Tl-weighted SE images. The C/N values for hepatic adenocarcinomas (seven metastases and one cholangiocarcinoma) and hemangiomas were larger for enhanced MT-GRE images (adenocarcinoma, 8.4 ± 2.3 [P < 0.01); hemangioma, 24 ± 2.1 [P < 0.05]) than for enhanced GRE images (5.0 ± 1.9 and 18 ± 2.7, respectively). These enhancing tumors had the highest scores in the qualitative analysis. Enhanced MT-GRE images showed no advantage for depiction of hepatocellular carcinomas relative to the other images.     

MR mammography: influence of menstrual cycle on the dynamic contrast enhancement of fibrocystic disease

Magnetic resonance mammography (MRM) provides data regarding the nature of tumours based on contrast medium dynamics; fibrocystic changes in the breast, however, may lead to false-positive results. This study investigated whether the contrast medium dynamics of fibrocystic changes are dependent on the menstrual cycle. Twenty-four patients with palpable lumps but normal mammographies and ultrasound studies were examined. The MRM technique was performed during the first and second part of the menstrual cycle using a FLASH 3D sequence, both native and at 1, 2, 3 and 8 min after intravenous application of 0.15 mmol/kg body weight of gadodiamide. The calculated time–intensity curves were evaluated based on the following criteria: early percentage of contrast medium uptake in relation to the native value; formation of a plateau phenomenon after the second minute; the point of maximal contrast medium uptake; and calculation of the contrast enhancing index. During the second half of the menstrual cycle, a generally greater contrast medium uptake was observed. Nevertheless, when further diagnostic criteria, such as continuous contrast medium increase as a function of time, were considered, there was no increased rate of false-positive findings. The phase of the menstrual cycle may affect the specificity of the examination, if only the quantitative contrast medium uptake and the percentage of contrast medium uptake in the first 2 min are considered. A control MRM during the other half of the cycle may then be indicated and additional diagnostic criteria may improve specificity. Received: 14 August 1997; Revision received: 5 December 1997; Accepted: 5 October 1998     

锰对比剂在胰腺MR增强扫描中的价值

目的　探讨胰腺腺细胞是否摄取锰福地匹三钠 [manganese (Ⅱ )N ,N′ dipyridoxylethlenediamine N ,N′ diacetate 5 ,5′ bisc(phosphate) ,简称Mn DPDP]或者其代谢产物。方法对 6只健康雄性家犬经十二指肠乳头插管制作人工胰瘘。按 2ml/kg经静脉以 2～ 3ml/min的流率滴注Mn DPDP ,于给药前、后收集胰液 ,采用原子吸收光谱法 (AAS)测量胰液中的锰含量。给药前及给药后约 30min行SET1WI及快速多平面扰相位梯度回波 (fastmultiplannarspoiledgradientrecallecho ,简称SPGR)T1WI上腹部横断面扫描。结果　给药后胰液中锰含量较给药前增加 (6 17× 10 -3 ～ 1 5 8×10 -2 )mmol/L(中位数 1 0 9× 10 -2 mmol/L) ,统计学上两者差异具有显著性意义 (Z =2 2 0 ,P <0 0 5 ) ;给药后胰腺信噪比于SET1WI及SPGRT1WI上分别上升 6 %～ 113% (中位数 5 0 % )和 18%～ 10 8% (中位数 6 5 % )。结论　实验结果表明胰腺腺细胞能摄取锰经胰液排泄 ,并在Mn DPDP增强MRI胰腺强化中起主导作用。Mn DPDP增强MRI胰腺显影提示该方法可用于胰腺疾病的诊断 ,并有评价胰腺外分泌功能的潜能。     

Contrast-enhanced MR imaging of liver and spleen: First experience in humans with a new superparamagnetic iron oxide

The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 μmol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration. MR imaging at 1.5 T was performed before and 8 hours to 14 days after fast intravenous injection (500 μmol Fe/min) of the SPIO (six subjects per dose). Results of this phase I study demonstrate that SHU 555 A at a concentration of 0.5 mol Fe/L was well tolerated. A dose-dependent minor increase in activated partial thromboplastin time, which remained within the normal range, was seen. All doses of SPIO caused a signal loss in both liver and spleen (P <.05) with a spin-echo sequence (TR = 2,300 msec, TE = 45 msec). The signal losses in the liver 8 hours after contrast agent injection were 58%, 79%, 82%, and 87% for the 5, 10, 20, and 40 μmol Fe/kg doses, respectively. The corresponding signal losses in the spleen were 23%, 45%, 65%, and 78%, respectively. The doses that reduced signal intensity by half were 3.1 μmol Fe/kg for the liver and 12.8 μmol Fe/kg for the spleen. The results suggest that the new SPIO formulation is a safe and efficient MR contrast agent.     

Detection of hepatocellular carcinoma: comparison of ferumoxides-enhanced and gadolinium-enhanced dynamic three-dimensional volume interpolated breath-hold MR imaging

The purpose was to compare the diagnostic accuracy of ferumoxides-enhanced MR imaging and gadolinium-enhanced dynamic MR imaging using three-dimensional (3D) volume interpolated breath-hold examination (VIBE) for the detection of hepatocellular carcinoma (HCC). Forty-nine patients with 61 HCCs, who underwent ferumoxides-enhanced and gadolinium-enhanced dynamic MR imaging, were included prospectively in this study. Ferumoxides-enhanced MR imaging was performed 24 h after completion of the dynamic study using 3D-VIBE. Three radiologists independently interpreted the images. The diagnostic accuracy was evaluated using the receiver-operating characteristic method, and the sensitivity of each imaging technique was compared using McNemars test. The mean diagnostic accuracy of dynamic MR imaging (Az=0.95) was higher than that of ferumoxides-enhanced MR imaging (Az=0.90), but failed to reach a statistical significance (P=0.057). The mean sensitivity of dynamic MR imaging (90.7%) was significantly superior to that of ferumoxides-enhanced MR imaging (80.9%, P=0.03). Furthermore, for lesions smaller than 15 mm, the mean sensitivity of dynamic MR imaging was significantly higher than that of ferumoxides-enhanced MR imaging (85.2% vs. 69.2%, P<0.05). Dynamic MR imaging showed a trend toward better diagnostic accuracy for than ferumoxides-enhanced MR imaging for the detection of HCCs.     

Added diagnostic value of T2-weighted MR imaging to gadolinium-enhanced three-dimensional dynamic MR imaging for the detection of small hepatocellular carcinomas

Purpose

To assess the added value of T2-weighted MRI to gadolinium-enhanced dynamic MRI for detection of HCCs.

Materials and methods

Two readers retrospectively analyzed MRIs of 115 patients with 131 HCCs (size; 0.6–2.0 cm) that had been diagnosed by histology (n = 41) or imaging findings (n = 90). Two separate blind image analyses of the gadolinium set and the combined T2-weighted imaging and gadolinium sets were performed. Diagnostic accuracy was evaluated using the alternative-free response receiver operating characteristic method with four-point scale. Sensitivity and positive predictive value were also calculated.

Results

For both observers, the Az values and sensitivities with the combined T2-weighed imaging and gadolinium set (mean Az 0.806, sensitivity 84.7) were significantly higher than those with the gadolinium set (mean Az 0.660, sensitivity 59.9) (p < 0.05). The addition of T2-weighted imaging led to a change in diagnosis for 27 lesions by both observers, which at gadolinium set were assigned a confidence level of 1 or 2 but at additional reading of T2-weighted imaging were assigned a confidence level of 3 or 4. For the positive predictive values, each image set showed a similar value for each observer.

Conclusion

The addition of T2-weighted imaging to gadolinium-enhanced 3D dynamic imaging could be helpful in the detection of HCC by increasing reader confidence for HCCs with equivocal findings on gadolinium-enhanced MRIs.     

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.