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.     

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.     

Chronic carbon tetrachloride and phospholipase D hepatotoxicity in rat: in vivo 1H magnetic resonance, total lipid analysis, and histology

Magnetic resonance (MR) imaging, localized in vivo proton spectroscopy, and T1 relaxation measurements were obtained from the livers of rats treated chronically with carbon tetrachloride and phospholipase D. The MR data correlated well with lipid changes measured biochemically and histologically. MR images appeared generally hyperintense during fatty infiltration, changing to hypointense mottling during cirrhosis. Water T1 relaxation times showed no statistically significant change at any time during the experiments from the control value of 908 ms (SE = 42 ms). Minor changes in lipid T1 values with time were noted. The average lipid T1 curve demonstrated a linear relation with time (r = 0.81), increasing from the control value of 283 ms (+/- 16 ms) to 365 ms (+/- 53 ms) at the end of the third week and decreasing slightly through the end of the experiment. Water-suppressed in vivo spectra showed quantitative changes in liver lipids which correlated well with the biochemical and histologic analysis. From the MR images and spectroscopy results it was possible to distinguish early fatty liver from more advanced cirrhosis.     

Influence of in vivo copper on MR images of the liver in rats

To investigate the effects of in vivo copper on magnetic resonance (MR) images, the authors studied Long-Evans cinnamon rats, which develop hepatitis and hepatocellular carcinoma as a result of abnormal copper metabolism. The livers of the rats were imaged before hepatitis developed; the absence of hepatic disease was confirmed histopathologically. The copper that accumulated in the liver of the rats was thought to exist in the form of divalent ions, which were suspected of reducing the T1 and T2 of neighboring protons. However, the signal intensities of the liver on T1- and T2*-weighted images did not change, suggesting that in vivo copper, even when accumulated abnormally, does not influence the signal intensity of MR images.     

Malignant hepatic tumors: Changes on MRI after hepatic arterial chemoembolization – preliminary findings

This study describes the MR appearances of malignant hypervascular liver lesions pre- and post-hepatic-arterial chemoembolization, with correlation to serial imaging and clinical responses. Eight patients with malignant hypervascular liver lesions underwent pretreatment and posttreatment MR examination on a 1.5-T MR imager. MR sequences included T1-weighted spoiled gradient echo (SGE), T2-weighted fat-suppressed spin echo or turbo spin echo, and dynamic gadolinium-enhanced SGE images. All patients underwent pretreatment, initial posttreatment, and subsequent posttreatment MR studies. The histology of primary tumors included various types of hepatocellular carcinoma (HCC) (four patients: fibrolamellar HCC [one patient], HCC [two patients], mixed HCC/cholangiocarcinoma [one patient]) and liver metastases (four patients: untyped islet cell tumor [two patients], gastrinoma [one patient], carcinoid [one patient]). Response to chemoembolization was determined by three assessments: MR response, serial imaging response, and clinical response. The appearance of MR response to chemoembolization was determined based on the correlation with clinical and serial imaging response. The MR response of lesions that showed good clinical response included: increase in signal intensity on T1-weighted images (three patients), decrease in signal intensity on T2-weighted images (three patients), and negligible or minimal enhancement on immediate postgadolinium images (four patients) after chemoembolization. The most marked change in lesion appearance was observed in lesions < 1 cm, which had intense homogeneous enhancement on pretreatment MR studies and negligible enhancement on initial posttreatment MR examinations. MR response of lesions that showed moderate clinical response demonstrated a variety of lesion appearances from substantial change to minimal change. MR response of lesions that showed poor clinical response demonstrated no change in lesion appearances compared with the pretreatment MR study. Our results demonstrated change in appearance of liver lesions between pre- and post-hepatic-arterial chemoembolization MR studies. MR response correlated with response determined by serial imaging studies and clinical findings.     

Spin-echo and dynamic gadoliniumenhanced flash MR imaging of hepatocellular carcinoma: Correlation with histopathologic findings

Evaluation of histologic subtype and degree of differentiation in hepatocellular carcinoma (HCC) is essential because it affects patient prognosis and treatment planning. To evaluate the histologic subtype of HCC with magnetic resonance (MR) imaging, conventional spin-echo and dynamic studies were correlated with histopathologic and angiographic findings in 72 HCCs. Dynamic MR imaging was performed with the fast low-angle shot (FLASH) technique after administration of gadopentetate dimeglumine. There was considerable overlap in signal intensity between various tumor grades on both T1- and T2-weighted images. On dynamic MR images, the peak contrast enhancement ratio correlated with tumor grade (well-differentiated, 29.5 ± 24.7; moderately differentiated, 63.5 ± 24.1; poorly differentiated, 86.9 ± 26.4) or degree of dilatation of the sinusoidlike vascular space between tumor cells. The maximum contrast-to-noise ratio in tumor (relative to surrounding liver) was achieved within 60 seconds in 45 HCCs (mostly of the trabecular or pseudoglandular type). Enhancement was slight or minimal in 17 tumors (mostly small, well-differentiated tumors). In 10 tumors, the degree of enhancement increased with time, with maximum enhancement in the delayed phase (most frequently in scirrhous HCC). These dynamic patterns correlated with angiographic findings. These data indicate that the degree and pattern of enhancement on dynamic MR images reflect tumor differentiation and architecture of HCC.     

家兔超急性期放射性肝损伤MRI表现与病理对照研究

目的　探讨超急性期放射性肝损伤MRI表现及其病理基础 ,评估MRI平扫及菲立磁增强扫描检出放射性肝损伤的时间效能。材料与方法　 18只家兔随机分成 3组后均给予 4 0Gy单次X线半肝照射 ,第 1组于照射后第1d、第 2、3组分别于照射后第 2、3d行肝区MRITSE T2 WI及TSE T1WI两个序列的平扫及菲立磁增强扫描 ,同时取材做组织学检查。对MRI表现与病理组织学检查结果进行对照分析。结果　所有家兔T2 WI及T1WI平扫、T1WI菲立磁增强扫描肝组织信号强度均未发现变化。T2 WI菲立磁增强扫描对放射性肝损伤的检出时间为照射后第 3d(P <0 .0 1) ,表现为肝组织信号强度受照区与非受照区均较T2 WI平扫时降低 ,但受照区肝组织信号强度较非受照区高 ,两者间可见分界线。所有家兔受照区肝组织在光镜下未见明确组织水肿、纤维化及炎症细胞浸润等病理征象 ,但其单位视野面积内含有SPIO颗粒的Kupffer细胞数在照射后第 3d明显低于非受照区 (P <0 .0 1)。电镜下 ,照射后第 3d的受照区肝细胞及Kupffer细胞内见线粒体明显肿胀伴局部空泡样变。结论　T2 WI菲立磁增强扫描在照射后短时间内 (照射后第 3d)即可检出超急性期放射性肝损伤 ,并能提供直观、精细的影像学依据     

Multinodular focal fatty infiltration of the liver: atypical imaging findings on delayed T1-weighted Gd-BOPTA-enhanced liver-specific MR images

We report a case of pathologically confirmed multinodular focal fatty infiltration. MRI was performed after bolus injection of gadobenate dimeglumine (Gd-BOPTA, MultiHance; Bracco, Milan, Italy), a liver-specific paramagnetic, gadolinium (Gd)-based MR contrast agent that concomitantly enables the acquisition of a standard dynamic phase with timing strategies similar to those used for other extracellular fluid contrast agents, followed by a delayed T1-weighted liver-specific phase (the so-called hepatobiliary phase). In the present case, multiple rounded areas of fatty infiltration, although confidently diagnosed using chemical shift sequences due to a significant signal intensity reduction on out-of-phase images, were unexpectedly hypointense during the delayed liver-specific phase of Gd-BOPTA. Reduced Gd-BOPTA concentration during the liver-specific phase is generally correlated with liver malignancy. Since such lesions can be prospectively mistaken for metastatic disease, we performed a hepatic biopsy to establish a definitive diagnosis. Our empirical observations suggest that Gd-BOPTA uptake may be impaired in fatty infiltrated liver tissue. Because at present there is no report evaluating the kinetics of Gd-BOPTA in fatty liver, further studies are needed to specifically investigate this issue.     

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.     

Fatty liver. Chemical shift phase-difference and suppression magnetic resonance imaging techniques in animals, phantoms, and humans.

In vitro animal and human models were used to evaluate the potential of chemical shift magnetic resonance imaging (MRI) for assessing fatty liver. Phantoms of varying fat content were created from mayonnaise-agar preparations. Fatty liver was induced in eight rats by feeding them ethanol for three to six weeks (36% of total calories), whereas eight control rats were fed a normal diet. T1-weighted in-phase and opposed-phase MR images were obtained of the phantoms animals, and 28 human subjects. Additional images obtained in animals included long TR images with in-phase and opposed-phase technique, and hybrid chemical shift water and fat suppression. The rats were killed and histologic status was graded blindly by a hepatopathologist as normal, mild, moderate, or severe fatty change, for correlation with MR grading. Quantitative analysis of MR images included fat signal fraction for animals, and relative signal decrease between in-phase and opposed-phase images for phantom and human data. Phantom in-phase signal increased linearly with respect to fat content, whereas opposed-phase signal decreased linearly. MRI and histologic grading of rat livers were highly correlated, especially when based on water suppression images (r = 0.91, P = .0001). Opposed-phase images were also highly correlated, while fat suppression images were less effective. There was no overlap between MR-derived fat fractions for control (2.6%-5.7%) versus ethanol-fed rats (7.7%-17.9%, P = .0002). Human liver considered to be fatty by visual inspection (n = 8) had higher relative signal decrease than nonfatty liver (n = 22) (P less than .001). Phantom, animal, and human data demonstrate that comparison of T1-weighted in-phase and opposed-phase images is both practical and sensitive in the detection and grading of fatty liver.     

Mr imaging of hepatic nodular regenerative hyperplasia

Nodular regenerative hyperplasia (NRH), a rare condition that is commonly associated with noncirrhotic portal hypertension, is not well described in the MR literature. Three patients at two institutions were identified who had both abdominal MR imaging and pathologic evidence of NRH. All examinations were performed at 1.5 T and included axial T1- and T2-weighted spin-echo (SE) images. The MR studies were reviewed by two radiologists in consensus. Two patients had multiple liver lesions that had high signal components on T1-weighted images and were predominantly isointense with liver on the T2-weighted images. One patient had no focal lesions identified. NRH, when visualized on MR images, appears as multifocal masses with shortened Tl and T2 similar to liver. NRH should be considered in the differential diagnosis of hepatocellular tumors, especially in patients with a predisposing condition.     

Proton chemical shift imaging: an evaluation of its clinical potential using an in vivo fatty liver model

The potential laboratory and clinical utility of proton chemical shift imaging (PCSI) was evaluated by studying fatty liver change in rats, which offered a simple animal model for tissue lipid buildup. There was excellent correlation between lipid group signal intensities from in vivo PCSI studies and liver triglyceride levels obtained from in vitro measurements (R = 0.97). The in vivo T1 relaxation time measurements in fatty liver tissue demonstrated two distinct populations of nonexchanging protons. We explain the reason for the lack of sensitivity in conventional magnetic resonance (MR) imaging studies of fatty liver change and discuss the implications of our findings for MR imaging studies of other tissues. PCSI promises improved diagnostic sensitivity and specificity in studying a wide range of human pathologic conditions.     

Quantitative mr imaging data in the evaluation of hepatic metastases during systemic chemotherapy

To identify changes induced by chemotherapy in hepatic metastases, 34 patients with metastases underwent magnetic resonance (MR) imaging before the start of systemic chemotherapy and monthly thereafter. The number, size, and morphologic patterns of the lesions and changes in quantitative parameters (signal-to-noise ratio [S/N], contrast-to-noise ratio, and signal intensity ratio) were evaluated and correlated with response to treatment and prognosis. After treatment, seven patients showed a partial response, 18 had stable disease, and nine had progressive disease. No relevant changes in the patterns of the lesions were observed. Quantitative data showed that patients with a good prognosis had an increase in S/N on T1-weighted images and a relative decrease on T2-weighted images; patients with a poor prognosis showed a decrease in S/N on T1-weighted images and an increase on T2-weighted images. The differences between patient groups were significant for both T1- and T2- weighted images. This study demonstrates the value of MR imaging in follow-up of liver metastases and suggests the usefulness of quantitative MR imaging data.     

Focal manifestations of diffuse liver disease at MR imaging.

Detection and exclusion of focal liver lesions is especially difficult in patients with diffuse liver disease. Magnetic resonance (MR) imaging may be particularly valuable in these patients. By judicious comparison of appropriate pulse sequences, normal and hypertrophic liver may be distinguished from atrophic, neoplastic, or otherwise abnormal hepatic parenchyma. Chemical shift (lipid-sensitive) techniques allow definitive identification of fatty liver, including focal fatty infiltration or focal sparing. T2-weighted and T2*-weighted images allow identification of iron overload, depicting malignancies as focal masses without iron. Analysis of signal intensity and internal morphology allows confident distinction between regenerative nodules and hepatocellular carcinoma in most instances, and allows diagnosis of early carcinoma within regenerative nodules. MR imaging provides capabilities for noninvasive characterization of liver tissue beyond those available with other noninvasive modalities.     

Malignant lesions of the liver identified on T1- but not T2-weighted MR images at 1.5 T

The authors reviewed their 21/2-year experience with a magnetic resonance (MR) imaging protocol for a 1.5-T MR imager that included T2-weighted fat-suppressed spin-echo, T1-weighted breath-hold gradient-echo, and serial dynamic gadolinium-enhanced T1-weighted gradient-echo imaging to identify histologic types of malignant liver lesions more apparent on T1- than on T2-weighted images. MR images of 212 consecutive patients with malignant liver lesions were reviewed. T2-weighted, T1-weighted, and dynamic contrast-enhanced T1-weighted images were examined separately in a blinded fashion. Seven patients demonstrated liver lesions (lymphoma [two patients] and carcinoid, hepatocellular carcinoma, colon adenocarcinoma, transitional cell carcinoma, and melanoma [one patient each]) on T1-weighted images that were inconspicuous on T2-weighted images. In all cases, the lesions were most conspicuous on T1-weighted images obtained immediately after administration of contrast agent. Histologic confirmation was present for all seven patients. The consistent feature among these lesions was that they were hypovascular, due either to a fibrous stroma or to dense monoclonal cellularity. These results suggest that in some patients with hypovascular primary neoplasms, the lesions may be identified only on T1-weighted images, and that immediate postcontrast T1-weighted images are of particular value in demonstrating lesions.     

Invited. Hepatitis,cirrhosis, and hepatoma

Virus hepatitis and liver cirrhosis are found at high incidence in Asia, and they require not only biochemical examination of blood but also subsequent imaging, because they are often complicated by hepatocellular carcinoma (HCC). It is, therefore, very important to know the specific appearances of hepatitis, liver cirrhosis, and HCC when we diagnose these diffuse liver diseases. Liver necrosis due to severe hepatitis is seen as high intensity on T2-weighted spin echo images. Regeneration is seen as low intensity on T2-weighted images. Morphologic and pathologic changes of cirrhotic liver are well demonstrated by MR imaging techniques. Fibrotic septum with inflammatory cell infiltration or rich pseudo bile duct show high intensity on T2-weighted images, and regenerating nodules shows low intensity. Gradient echo images show regenerating nodules with iron deposition as low-intensity nodules due to susceptibility artifact. MRI also has the potential to evaluate function of diffuse liver disease, cirrhosis, and hepatitis. MRI can visualize and diagnose HCC objectively. Dynamic MRI is very useful for diagnosing HCC. It is also applied for evaluation of effect after transcatheter arterial chemoembolization, because it shows enhancement only in the viable region at an arterial phase. MRI is less invasive and is thus an extremely important form of liver imaging.     

MR imaging assessment of experimental hepatic dysfunction with mn-DPDP

Manganese (II) N, N'-dipyridoxylethylenediamine-N, N'-diacetate 5,5′-bis(phosphate) (DPDP) is a paramagnetic magnetic resonance (MR) contrast agent that enhances the liver and is predominantly excreted through the biliary tree. The authors evaluated its utility in diffuse liver disease by assessing liver and gallbladder enhancement in 24 rabbits. Total (n = 6) or segmental (n = 6) biliary occlusion or galactosamine-induced hepatitis (n = 6) was induced 3 days before imaging. Six rabbits served as normal controls. T1- and T2-weighted axial MR images were acquired at baseline, followed by T1-weighted images every 10 minutes for 1 hour after the intravenous administration of 20 μmol/kg Mn-DPDP. Except for the segmental occlusion group, the baseline study did not allow distinction between normal and abnormal livers. The temporal hepatic enhancement pattern was statistically different for each group. The normal, segmental occlusion, and hepatitis groups showed patterns similar to one another but markedly higher signal intensity than the total-occlusion group throughout the observation period. In contrast, the gallbladder showed a greater difference in both degree of enhancement and time to peak enhancement among the four groups. Mn-DPDP produces a temporal hepatic enhancement pattern that allows recognition of markedly impaired livers, and gallbladder enhancement patterns that allow distinction of more subtly impaired livers.     

同相位与反相位梯度回波T_1WI在肝脏的应用价值

目的　评估同相位与反相位梯度回波T1WI在肝脏应用的价值 ,尤其是评估其对肝内脂肪变的检测能力。方法　 76例病人采用屏气同相位与反相位T1W梯度回波序列对肝脏扫描。将76例病人分成 3组分析 :(1)肝内无占位病变组 ,8例 ;(2 )肝癌组 ,34例 ;(3)血管瘤或囊肿组 ,共 34例。对 2种序列的图像进行了定量分析。结果　 76例中发现 14例肝脂肪变 ,6 2例无脂肪变。在 14例肝脂肪变中 ,反相位MRI还显示了 4例低信号肿块周边环状高信号带 ,其中 3例肝癌 ,1例血管瘤。在肝脂肪变的反相位上显示肝与脾和病灶信噪比或对比信噪比值较同相位低 ,但肝与脾和病灶间信噪比 (SNR)或对比信噪比 (CNR)在同相位与反相位上均无显著性差异 (P >0 .0 5 )。结论　同相位与反相位对显示肝脏病变和对脂肪成分的诊断是有价值的。两者互补 ,缺一不可。为避免肝脏病变在T1WI上的误诊或漏诊 ,建议常规行同相位与反相位T1W扫描     

CT and MR imaging of fatty tumors of the liver

The presence of fat in hepatic masses narrows the range of differential diagnoses down to hepatic angiomyolipoma, lipoma, adenoma, hepatoma, metastatic fatty tumors of the liver, focal fatty infiltration of the liver, and extrahepatic fatty masses such as intraperitoneal implants from malignant teratomas, and packed omentum. We report six hepatic tumors containing fat (lipoma, hepatocellular carcinoma, and calcified mass with fat-fluid level) with CT and magnetic resonance (MR) imaging. The distribution of fat was diffuse in the lipomas and some hepatocellular carcinomas and localized in other hepatocellular carcinomas and fat-fluid masses. The density ranged from - 100 to 0 HU. High intensity areas on both T1- and T2-weighted MR images corresponded to the hypodense areas on CT.     

化学位移成像和反转恢复快速自旋回波成像在肝脏的应用价值

目的 评价化学位移成像和反转恢复快速自旋回波对肝脏病变的检出能力。材料与方法 45例肝脏病变患者在进行常规SE T1WI和半傅立叶采集单次激发快速自旋回波（half-fFourier acquistition single-shot turbo spin-echo,HASTE)T2WI的同时,加用化学位移成像T1WI和反转恢复HASTE（IR－HASTE）T2WI。比较图像的信噪比（SNR）、肝脾对比噪声比（L－S CNR）、病灶对比噪声比（CNR）及病灶检出率。结果 化学位移成像T1WI的SNR、L－S CNR及SE T1WI均无显著性差异（P＞0．05）,但却能检出SET1WI无法显示的局灶性脂肪浸润和脂肪肝。IR－HASTE的SNR与HASTE相近（P＞0．05）,前者的L－S CNR及实性病灶的CNR均显著高于后者（P＜0．05）,特别是对较小的实质性病灶。结论 化学位移成像T1WI能提高肝脂肪成分的检出率,IR－HASTE的SNR与HASTE相近（P＞0．05）,前者的L－S CNR及实性病灶的CNR均显著高于后者（P＜0．05）,特别是对较小的实质性病灶。结论 化学位移成像T1WI能提高肝脂肪成分的检出率,IR－HASTE能提高肝实性病变的检出率,两种成像方法可作为常规肝脏检查方法的有力补充。