大鼠肝癌模型LAC-BSA-SPIO增强MR成像研究

目的：探讨LAC-BSA-SPIO对检出肝脏病灶,尤其是微小病灶的潜在价值及其对病灶良恶性鉴别诊断的价值。方法：建立大鼠肝硬化肝癌模型,分别测试LAC-BSA-SPIO最佳注射剂量和最佳扫描时间。28只大鼠MRI平扫序列为SET2map、FSET2WI、SET1WI、FRFSET2WI、GRE、3DFIESTA、SWI,注射LAC-BSA-SPIO（50μmolFe/kg）后30min行增强扫描。结果：成功建立大鼠肝硬化肝癌模型28只,共检出≥2mm的病灶63个,包括36个为肝细胞癌（HCC）,19个腺瘤性增生结节（AHN）,8个炎症性肌纤维母细胞瘤（IMT）。CNR最高的是50μmolFe/kgLAC-BSA-SPIO组;CNR最高的是30min组。增强扫描后AHN、IMT和HCC之间的T2值差异有显著性意义（P〈0.05）。SNR下降最明显的依次是GRE、3DFIESTA、FSET2WI、FRFSET2WI。在所有的序列上,HCC、AHN、IMT增强扫描前后的CNR差异均有显著性意义,所有序列增强扫描前后的差值在HCC、AHN、IMT之间差异有显著性意义（P〈0.05）。结论：LAC-BSA-SPIO有助于提高肿瘤-肝脏的CNR,对于肝硬化性肝癌的病灶有较高的鉴别诊断价值;最佳剂量为50μmolFe/kg,最佳扫描时间为静脉注射后30min。     

Evaluation of superparamagnetic iron oxide for MR imaging of liver injury: proton relaxation mechanisms and optimal MR imaging parameters.

PURPOSE: To investigate the proton relaxation mechanisms and the optimal MR imaging parameters in superparamagnetic iron oxide (SPIO)-enhanced MR imaging of liver injury. METHODS: A liver injury model was created in the rat using carbon tetrachloride. The T1 and T2 relaxation effects of SPIO in normal and injured liver were estimated by ex vivo relaxometry. In vivo laser confocal microscopy of the liver was performed to simulate the distribution and clustering of SPIO particles in the hepatic macrophages. SPIO-enhanced MR imaging (1.5T) of normal and diseased rats was performed with variable parameters. The liver specimens were prepared for histopathological examination. RESULTS: Histopathological and laser confocal microscopic findings showed diffuse macrophage distribution but decreased intracellular clustering of SPIO in injured liver. Ex vivo relaxometry showed sustained T1 and T2 relaxation effects of SPIO in liver injury. On MR images obtained with moderate echo time (spin echo [SE] 2000/40 and gradient echo [GRE] 130/9.0/60 degrees), injured liver showed significantly lower decrease in signal-to-noise ratio (SNR) than the normal liver, whereas little difference in SNR was found between the normal and injured liver on heavily T2-(SE 2000/80) and T1-weighted (SE 300/11 and GRE 130/2.0/90 degrees) MR images. CONCLUSION: Pulse sequences with a moderately long echo time (TE) may be more appropriate than heavily T1- or T2-weighted images for distinguishing normal and injured liver in SPIO-enhanced MR imaging because of the maintained T1 and T2 relaxation effect but decreased T2* relaxation effect of SPIO in injured liver.     

Evaluation of hepatocyte-specific paramagnetic contrast media for MR imaging of hepatitis

The hepatocyte-specific paramagnetic magnetic resonance (MR) contrast agents manganese-DPDP [N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′ bis-(phosphate)] and gadobenate dimeglumine were used for diagnosing chemically induced hepatitis in rats. Ex vivo liver tissue relaxation times and in vivo MR image signal-to-noise ratios were compared before and after contrast agent administration. Ex vivo relaxometry and in vivo MR imaging showed that Mn-DPDP enhanced normal and diseased livers to the same degree at all time points from 5 to 120 minutes. Gadobenate dimeglumine showed reduced T1 and T2 enhancements in hepatitis relative to those of normal liver, in the early phase (5–30 minutes). However, these effects are offsetting, and as a result, MR imaging failed to allow distinction of diseased from normal livers. This surprising result observed in vivo was in fact predicted by applying the Bloch equation to our ex vivo data. Our results show that detection and quantitation of hepatitis with MR imaging enhanced with paramagnetic cellspecific contrast agents will be more difficult than anticipated.     

SPIO与Gd-DTPA联合增强检测大鼠肝癌病灶的实验研究

目的 :观察联合使用SPIO和Gd DTPA对大鼠肝癌模型的增强特点。材料和方法 :制作 3 0只大鼠肝癌模型 ,增强前后行MR扫描 ,平扫序列包括SE、TSE、GRE的T1、T2WI序列。增强扫描分为 4组 ,其中Gd +SPIO联合增强组 10只 ,先注射Gd DTPA ,行SE、GRET1WI扫描 ,随后给予SPIO造影剂 ,扫描序列同平扫 ;SPIO +Gd联合增强组 10只 ,先注射SPIO ,行SE、GRET1WI扫描 ,12min后再给予Gd DTPA ,扫描序列同平扫 ;Gd、SPIO增强组各为 5只 ,增强扫描序列同平扫。分析各增强扫描组中病灶的增强特点。结果 :两种联合增强方法中 ,肝脏信号强度在所有扫描序列中均较平扫时下降 ,但与SPIO增强组无差异 ;病灶的SNR、CNR在SE、GRET1WI中明显高于平扫和SPIO、Gd DTPA增强法 ;在T2WI中病灶的SNR、CNR和单独使用SPIO无显著性差异。两种联合增强方法之间的SNR和CNR在每种扫描序列中没有显著性差异。结论 :SPIO和Gd DTPA联合增强方法利用了两种造影剂的优势 ,增加了肿瘤病变的对比 ,可提高发现病变的几率。     

半乳糖基白蛋白-超顺磁性氧化铁在兔肝脏小肿瘤检出中的应用价值

目的 初步探讨半乳糖基白蛋白-超顺磁性氧化铁(Gal-BSA-SPIO)在肝脏小肿瘤检出中的应用价值.方法 用半乳糖基白蛋白包被小粒径超顺磁性氧化铁(SPIO)制备Gal-BSA-SPIO,测定其粒径大小.建立兔VX2肝癌模型(肿瘤直径＜1.5 cm),用数字表法随机分为Gal-BSA-SPIO和SPIO组,每组10只,每组再分为5和10 μmol Fe/kg组,每组5只.所有实验动物均分别采用SE T2WI、快速自旋回波(FSE)T2WI和梯度回波(GRE)T2WI序列行MR平扫,并按实验分组行增强扫描,分别测量增强前后兔肝脏信噪比(SNR)和肿瘤与肝脏对比噪声比(CNR),并采用方差分析进行比较.扫描完毕后对肝脏及肿瘤组织进行病理检查.结果 Gal-BSA-SPIO平均粒径为34.4 nm,核心粒径为14.8 nm.5 μmol Fe/kg SPIO、5 μmol Fe/kg Gal-BSA-SPIO、10 μmol Fe/kg SPIO和10 μmol Fe/kg Gal-BSA-SPIO 4组增强前后肝脏SNR差值SE序列分别为(1.92±0.42)、(3.75±0.51)、(3.25±0.72)、(4.73±0.34),FSE序列分别为(1.56±0.18)、(3.56±0.64)、(3.33±0.16)、(4.83±0.16),GRE序列分别为(5.55±0.91)、(9.58±0.66)、(9.20±0.29)、(10.63±0.32),不同对比剂及不同序列组间比较差异均有统计学意义(P值均＜0.01).上述4组增强前后肿瘤与肝脏CNR差值SE序列分别为(2.22±0.68)、(5.27±0.22)、(4.25±0.51)、(6.97±0.63),FSE序列分别为(1.73±0.41)、(4.46±0.54)、(3.73±0.49)、(5.39±0.39),GRE序列分别为(5.98±0.71)、(11.79±0.57)、(9.57±0.54)、(14.64±1.35),不同对比剂及不同序列组间比较差异均有统计学意义(P值均＜0.01).Gal-BSA-SPIO主要作用于肝实质细胞,而SPIO主要分布于Kupffer细胞内.结论 Gal-BSA-SPIO具有良好的负向肝脏强化效应,对肝内小肿瘤的检出具有良好的潜在应用价值.     

Performance of Gd-EOB-DTPA and superparamagnetic iron oxide particles in the detection of primary liver cancer: A comparative study by alternative free-response receiver operating characteristic analysis

The performance of gadolinium-ethoxybenzyl-dieth-ylenetriaminepentaacetic acid (Gd-EOB-DTPA) and superparamagnetic iron oxide (SPIO) particles in detecting liver cancer was compared using alternative free-response receiver operating characteristic (AFROC) analysis, which allowed observers to indicate both the confidence level and the locations of all perceived abnormalities. Axial T1-weighted MR images (1.5 T) pre/post Gd-EOB-DTPA (25 μmol/kg) injection were obtained for 12 rats with chemically induced liver tumors (64 tumors). T2-weighted images (T2WI) were obtained pre/post SPIO (10 μmol/kg) injection for the same animal. Liver signal-to-noise ratio (SNR), tumor-liver contrast-to-noise ratio (CNR), and histopathologic sections corresponding to MR images were obtained. In AFROC, the location and the confidence level for each tumor were indicated independently on MR images by four radiologists. By plotting true-positive fraction and probability of false-positive per image, the area under the AFROC curve (A1) was estimated and statistically analyzed between each sequence. Either drug significantly improved tumor-liver CNR (P < .001) and tumor detection (diameter ≤ 6 mm; P < .05). Gd-EOB-DTPA significantly (P < .05) improved the A1 in T1WI. There was no A1 difference between T2WI + SPIO and T1WI + Gd-EOB-DTPA. Gd-EOB-DTPA-enhanced T1WI showed the same performance as SPIO-enhanced T2WI in detecting liver tumors.     

Enhanced tumor detection in the presence of fatty liver disease: Cell-specific contrast agents

It is assumed that hepatobiliary, cell-specific contrast agents will be adversely affected by the presence of diffuse liver disease. The diagnostic efficacy for tumor detection in the presence of fatty liver disease was experimentally studied at contrast-enhanced magnetic resonance (MR) imaging with manganese-DPDP (N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis[phosphate]) and gadobenate dimeglumine (Gd-BOPTA/dimeg) and compared with conventional and chemical shift imaging. Carcinosarcoma was implanted into the liver of rats, and fatty liver was induced with L-ethionine. Without contrast agents, the tumor-fatty liver contrast-to-noise ratio (C/N) was increased on T1-weighted and decreased on T2-weighted MR images relative to tumor-bearing control rats without fatty liver. Chemical shift imaging (phase-contrast method) increased the tumor—fatty liver C/N from 2.3 ± 1.0 to 6.1 ± 1.7 (P <.001). Mn-DPDP and Gd-BOPTA/dimeg increased the tumor—fatty liver C/N from -5.4 ± 1.6 to -11.0 ± 1.9 and ?9.8 ± 3.4, respectively (P <.001). The hepatobiliary, cell-specific contrast agents were equally effective in both fatty and nonfatty liver and outperformed both chemical shift and conventional MR imaging in detecting liver tumors.     

Dual-contrast MR imaging of liver cancer in rats

MR contrast agents increase hepatic tumor conspicuity, as measured in terms of contrast-to-noise (C/N) ratios. With an animal model of hepatic metastases from breast cancer, IV administration of Gd-DTPA (0.2 mmol/kg) shows a biphasic time response, transiently increasing the signal intensity of liver relative to tumor, with C/N ratio magnitudes increasing from -5.7 to -16.3 (SE 250/20); after a delay, the signal intensity of tumor increases relative to liver with a reversal of the C/N sign from negative to positive and an increase in the C/N magnitude to +25.0. IV administration of ferrite particles (0.05 mmol Fe/kg) shows a monophasic time response, increasing signal intensity of tumor relative to liver from +1.5 to +49.5 (SE 500/30). When both contrast agents were administered together (dual-contrast technique), the tumor-liver C/N magnitude reached a maximum of +67.8 (SE 500/30) 12 min after drug infusion. Analysis of individual contrast and noise factors contributing to this technique revealed a strong correlation between the signal intensity of liver and the signal intensity of ghost artifacts, which increase after administration of Gd-DTPA (r = .89) and decrease after administration of ferrite (r = 1.0). Dual-contrast imaging shows a synergistic addition of contrast and suppression of noise from ghost artifacts, maximizing the C/N and increasing the conspicuity of focal liver lesions.     

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.     

Ferrite-enhanced MR imaging of hepatic lymphoma: an experimental study in rats

The purpose of this investigation was to define the potential of unenhanced and ferrite-enhanced MR to detect hepatic lymphoma. Rats were implanted with diffuse and focal hepatic lymphoma. Both in vitro measurements of relaxation times and in vivo MR imaging of normal liver and of diffuse and focal hepatic lymphoma were compared. Diffuse infiltrative hepatic lymphoma showed increased T1 (45%) and T2 (41%) relaxation times in vitro, but could not be distinguished from normal control livers on in vivo spin echo (SE) images with a repetition time of 500 msec and an echo time of 30 msec (SE 500/30) or SE 1500/60 images. Focal hepatic lymphoma showed increased T1 (185%) and T2 (115%) relaxation times relative to normal liver tissue. Focal hepatic lymphoma was undetectable on unenhanced SE 500/30 MR images (contrast-to-noise ratio, C/N = 0.4) and was slightly hyperintense on SE 1500/60 images (C/N = 1.1). Ferrite (50 mumol Fe/kg) was administered to improve tissue contrast. In normal control animals, T2 of liver in vitro decreased from 29.3 +/- 3.3 msec to 11.1 +/- 1.2 msec, and image signal-to-noise ratio (S/N) of liver in vivo decreased from 16.1 +/- 2.4 to 2.8 +/- 0.3 (p less than .005). Ferrite-enhanced diffuse hepatic lymphoma showed in vitro T2 values and in vivo MR image S/N values indistinguishable from those of normal control animals. The T2 of focal hepatic lymphoma was essentially unaltered by ferrite. On SE 500/30 images, focal hepatic lymphoma became readily detectable, quantitated by a 35-fold increase in tumor-liver C/N. We conclude that clinical studies are warranted to determine the value of ferrite enhanced MR as a technique for the enhanced detection of focal hepatic lymphoma.     

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.     

Detection of hepatic metastases with MR imaging: spin-echo vs phase-contrast pulse sequences at 0.6 T

The purpose of this study was to compare the sensitivity of T1-weighted and T2-weighted spin-echo (SE) pulse sequences with T2-weighted phase-contrast (PC) imaging techniques for the detection of hepatic metastases. Pulse-sequences performance was evaluated in 52 consecutive patients with 88 hepatic metastases who underwent MR imaging at 0.6 T. Lesion-liver contrast-to-noise ratios (CNR) on SE 260/14 (-12.4 +/- 6.7) and PC 2350/60 (+10.8 +/- 4.2) images were significantly (p less than .05) greater than on SE 2350/60 (+ 7.8 +/- 3.9), SE 2350/120 (+8.1 +/- 4.8), SE 2350/180 (+7.9 +/- 4.5), and PC 2350/30 (+4.6 +/- 2.9) images. Sensitivity for detection of 88 individual metastases was comparable on SE 260/14 (78 of 88 patients) and PC 2350/60 (81 of 88 patients) images and was significantly (p less than .05) greater than on in-phase T2-weighted SE images (TE = 60, 70 of 88 patients; TE = 120, 69 of 88 patients; TE = 180, 65 of 88 patients). Histologic analysis of tumor-free liver showed fatty change in 11 of 13 specimens available for pathologic evaluation. In all 11 of those patients, PC images increased tumor-liver contrast in comparison with the in-phase SE images. This analysis suggests that for detection of hepatic metastases at midfield strengths, the T1-weighted, short TR/short TE (SE 260/14) and the T2-weighted, phase-contrast (PC 2350/60) pulse sequences offer comparable performance.     

Liver-specific MR contrast agents: current status and prospects]

Liver-specific MR contrast agents include superparamagnetic iron oxide (SPIO) particles and hepatobiliary paramagnetic agents. SPIO particles are phagocytosed by reticuloendothelial cells in the liver, resulting in negative enhancement of the liver parenchyma on T2- or T2*-weighted images. Ferumoxides and related iron oxide formulations have been tested clinically throughout the world, and have been demonstrated to improve the detection and characterization of hepatic neoplasms. Hepatobiliary paramagnetic agents are partially taken up by hepatocytes, yielding positive, sustained enhancement of the liver parenchyma on T1-weighted images. These agents are referred to as "value-added" versions of extracellular gadolinium compounds because they increase tumor-liver contrast in both the perfusion phase and hepatobiliary phase. Although only ferumoxides are currently available for clinical use, many agents are in the pipeline. The possibility of "one-stop shopping" diagnosis by liver-specific MR contrast agents is an attractive alternative to the existing multistep diagnosis in liver imaging. Further studies to analyze the cost-benefit ratio will follow, to determine whether liver-specific MR contrast agents lead to change in patient treatment and whether such a decision would be reliable.     

Phased array breath-hold versus non-breath-hold MR imaging of focal liver lesions: A prospective comparative study

This study was undertaken to determine whether phased array breath-hold T1- and T2-weighted sequences can replace non-breath-hold spin echo (SE) sequences in the imaging of focal liver lesions by comparing overall image quality, liver-lesion contrast, and artifact. Both breath-hold and non-breath-hold T1-weighted and T2-weighted imagings of focal liver lesions were prospectively compared in 120 patients with suspected focal liver lesions imaged at 1.5 T with use of a body phased array multicoil. Breath-hold images were acquired with T1-weighted fast low-angle shot (FLASH) and T2-weighted turbo spin echo (TSE) sequences, and non-breath-hold images were made with conventional T1- and T2-weighted SE sequences. Qualitative image analysis was done by three blinded readers, and quantitative analysis was done. The highest signal-to-noise ratios were obtained with breath-hold T1-weighted FLASH sequence. The signal-to-noise ratios of breath-hold T2-weighted TSE sequence were slightly inferior to those of non-breath-hold SE sequence. Both T1-weighted and T2-weighted breath-hold sequences had less image artifact. Overall image quality of breath-hold sequences was better than that of non-breath-hold sequences for both T1- and T2-weighted sequences (P < .01). The tissue contrast of T1-weighted FLASH sequence was superior to that of SE sequence (P < .01). On T2-weighted imaging, tissue contrast of solid lesions was better on conventional SE sequence than that on breath-hold TSE sequence (P < .01). Respiratory ghost artifact was less prominent on T1-weighted FLASH sequence, although this artifact was occasionally seen on breath-hold T2-weighted TSE sequence. In a state-of-art MR unit with use of a phased array multicoil, conventional T1-weighted can be replaced by breath-hold sequences. On T2-weighted imaging, because solid tumor-liver contrast on breath-hold TSE imaging is inferior to that on non-breath-hold SE image, breath-hold imaging may not replace conventional non-breath-hold T2-weighted SE sequence.     

Uptake of mangafodipir trisodium in liver metastases from endocrine tumors

The purpose of the study was to investigate retrospectively whether mangafodipir trisodium (MnDPDP) can enhance the liver metastases from endocrine tumors. Thirteen patients with endocrine tumors and liver metastases underwent T1-weighted spin-echo (SE) and turbo gradient-echo (GRE) MRI conducted before and 20 to 60 minutes after iv infusion of MnDPDP. Additional 24-hour-delay scans were performed in 8 of 13 patients. MR signal intensity (SI) was measured in liver parenchyma and metastases, which was then related to that of paraspinal muscle. A total of 30 lesions on precontrast and postcontrast images and 18 lesions on 24-hour-delay images were measured. An enhancement by 49% in SE and 40% in GRE images (P = .0001) was observed in tumor tissues after MnDPDP infusion. In 24-hour-delay images, the SI of the lesions remained relatively high, but in liver parenchyma, it decreased significantly, and the tumor-liver tissue contrast was reduced.     

Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for MR imaging of acute hepatitis in a rat model

This work was conducted to test the hypothesis that contrast-enhanced MRI with hepatocyte-specific contrast agents facilitates quantitation and mapping of diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine (Gd-BOPTA/Dimeg, Bracco SpA, Milano, Italy) is a new paramagnetic hepatocytespecific contrast agent currently undergoing clinical trials. We have assessed the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver diseases in a rat model of chemically induced hepatitis. The study was based on the measurements of in vivo liver relaxation times as well as on the acquisition of standard SE images. Acute hepatitis considerably reduced the degree of T1 shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images was inferior, in terms of both strength and duration, to that recorded in control rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our results show that gadobenate dimeglumine enhanced MR imaging has the potential for visualization of hepatitis and for assessment of liver function. Our conclusions differ from those previously published on this subject by other authors. The reasons that led to differing conclusions are discussed.     

Comparison between intravenous and intraarterial contrast injections for dynamic 3D MRI of liver tumors in the VX2 rabbit model

PURPOSE: To test the hypothesis that catheter-directed intraarterial (IA) contrast agent injection increases tumor enhancement and conspicuity compared to intravenous (IV) injection. MATERIALS AND METHODS: Eight VX2 liver tumors were grown in five rabbits. After positioning a catheter in the hepatic artery, we performed 3D inversion recovery GRE MRI after IA and IV gadopentetate-dimeglumine contrast injections at doses of 0.04 and 0.1 mmol/kg, respectively. Peak enhancement (signal-to-noise ratio (SNR)) and conspicuity (contrast-to-noise ratio (CNR)) were measured for each acquisition. RESULTS: The peak SNR and CNR were 21.7 +/- 5.8 and 17.0 +/- 4.8 (mean +/- SD) after IA injection, and 16.9 +/- 10.2 and 6.2 +/- 2.6 after IV injection. The IA CNR was significantly greater than the IV CNR (P < 0.05), with a >60% increase in CNR for each tumor. For six of the eight tumors the IA SNR was greater than the IV SNR, but statistical significance was not achieved due to the small sample size of the study (P = 0.07). CONCLUSION: We demonstrated the feasibility of using IA injection techniques to improve tumor conspicuity. This strategy could be employed to enhance the detection of small liver tumors or to conserve contrast agent in future MRI-guided transcatheter liver therapies.     

不同MR扫描序列在SPIO增强大鼠肝癌模型的对比研究

目的：比较多种扫描序列超顺磁氧化铁（SPIO）增强扫描对显示大鼠肝癌病灶的能力，找出最佳扫描方案。TSE T2WI、SE双回波的T2WI＋PDWI、GRE T1WI、T2^＊WI，分析增强前后大鼠肝癌病灶的强化特征，并进行病理学检查对照分析。结果：注射SPIO对比剂后，所有扫描序列均显示肝脏的信号强度较增强前有不同程度的下降，肝癌病灶CNR均分别高于平扫。增强后GRE T2^＊WI中病灶的CNR明显高于其它序列，但增强后TSE T2WI和常规SE T2WI在显示病变的SNR、CNR方面没有显著性差异。结论：SPIO增强后检测肝癌病灶的各种序列中，以GRE T2^*WI最为敏感，其次是双回波的T2WI＋PDWI序列。     

Evaluation of [Gd(Bz-TTDA)]2- as a potential contrast agent in MR imaging of the hepatobiliary system: an animal study

PURPOSE: To evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz-TTDA)]2- [(4s)-4-benzyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecandioic acid]2- designed for use as a hepatobiliary MR contrast agent. MATERIALS AND METHODS: MR imaging studies for normal and hepatocellular carcinoma (HCC) rat models were performed using a 1.5-T scanner. Sequential multislice T1-weighted turbo field echo (TFE) (TR/TE/flip angle: 15 msec/6.1 msec/25 degrees) coronal images of normal rats were obtained before and after intravenous injections of 0.1 mmol/kg [Gd(Bz-TTDA)]2- in study groups (N = 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd-DTPA)2- in control groups (N = 12). Similar protocols of MR imaging with additional T2-weighted images were used for the rats with implanted HCC in both study and control groups (N = 12, in each group). MR images were analyzed to evaluate the time-enhancement change (% increase of signal-to-noise ratio [SI/N]) in normal liver, renal cortex, renal medulla, and tumors. The liver-lesion contrast-to-noise ratios (CNR) were also evaluated in study and control groups. The rats were killed immediately after the last MR scan to undergo autopsy and histopathologic observation. The acute toxicity test (medial lethal dose, LD50) in mice was also done. RESULTS: The liver enhancement in normal rats reached a plateau 5-50 minutes after injection of [Gd(Bz-TTDA)]2-, maintained for three hours, then gradually declined. Intensity of enhancement in liver, renal cortex, and medulla after injection of [Gd(Bz-TTDA)]2- was significantly higher than with Gd-DTPA. The efficacy of tumor characterization with injection of [Gd(Bz-TTDA)]2- was similar to that of Gd-DTPA at the early dynamic phase of the contrast study. However, the liver-lesion CNRs were significantly higher in the study group in the later phase, when tumor enhancement decreased and liver enhancement persisted. The dose of LD50 in acute toxicity test of [Gd(Bz-TTDA)]2- in mice was 7.5 mmol/kg. CONCLUSION: The preliminary results in this animal study indicated that [Gd(Bz-TTDA)]2- has the potential of becoming a reliable liver MR contrast agent.     

Gd-BOPTA/Dimeg: experimental disease imaging.

The novel tissue-specific contrast agent, Gd-BOPTA/Dimeg, was tested in MR imaging of experimental focal liver disease and of acute myocardial ischemia in rats. Directly implanted liver tumors and blood-borne metastases were used as models for focal liver disease and occlusion of the lower anterior descending coronary artery as model for acute ischemia. The studies with implanted tumors, at a dose level of 250 mumol/kg, showed a very high (370%) and persistent (greater than 2 h) increase in the tumor-liver contrast-to-noise ratio (CNR), owing to selective enhancement of normal liver parenchyma signal intensity. While all blood-borne metastases showed a similar late CNR enhancement, some of them experienced early contrast loss due to transient signal intensity enhancement. In myocardial imaging, Gd-BOPTA/Dimeg produced a signal intensity enhancement in normal myocardium and an injured area-normal area CNR enhancement which were both much stronger and more persistent than those produced by Gd-DTPA/Dimeg.