New proposal for the staging of nonalcoholic steatohepatitis: Evaluation of liver fibrosis on Gd-EOB-DTPA-enhanced MRI

Purpose

We investigated whether the gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was useful for nonalcoholic steatohepatitis (NASH) staging based on the severity of liver fibrosis.

Materials and methods

Twenty-one male Sprague-Dawley rats aged 7 weeks, weighing about 150 g in NASH group were fed a choline-deficient diet for 4, 7 or 10 weeks, and seven rats in the control group were fed a standard diet (n = 7). After the feeding period, the rats were subjected to contrast-enhanced MRI (2D-FLASH; TR/TE = 101/2.9 ms, flip angle 90°). Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected at 24-h intervals, and the speed of contrast injection was 1 mL/s. Signal intensities of the liver were measured and the relative enhancement (RE), the time of maximum RE (T_max) and elimination half-life of RE (T_1/2) in the liver were compared. The fibrosis rate (%) was calculated with the following formula: fibrosis/whole area × 100.

Results

The fibrosis rates of each group were as follows: 0.52, 0.79, 2.84, and 0.50% (4, 7, 10 weeks and control groups). The fibrosis rate of the 10 weeks group was significantly higher than the control and 4 or 7 weeks groups. Although there was no difference between the T_max and T_1/2 of each group after Gd-DTPA injection, the T_max and T_1/2 of the 10 weeks group were significantly prolonged in comparison with the control and 4 or 7 weeks groups after Gd-EOB-DTPA injection (p < 0.01). There was a significant correlation between the fibrosis rate and T_max or T_1/2 after Gd-EOB-DTPA injection (r = 0.90 or 0.97).

Conclusion

It was possible to assess the progress of liver fibrosis in NASH by evaluating the signal intensity-time course on Gd-EOB-DTPA-enhanced MRI.     

DSA和钆塞酸二钠增强MRI对肝癌术后复发微小病灶诊断的比较研究

目的 对比研究DSA和钆塞酸二钠(Gd-EOB-DTPA)增强MRI对肝癌术后复发微小病灶的诊断效能,评估其诊断价值.方法 回顾性分析2011年9月至2016年3月收治的肝癌术后怀疑有微小复发病灶的患者38例,所有患者均经过DSA、DSA碘油CT和Gd-EOB-DTPA增强MRI检查,对比分析各检查方法诊断的阳性和阴性病例,计算诊断的灵敏度和特异度,所有病例均由2名放射科副主任医师根据诊断标准独立诊断,以手术或者穿刺病理结果以及至少6个月随访作为最终诊断依据.结果 38例患者,共发现47个病灶,病灶直径0.5～2.0 cm,平均(1.2±0.8)cm,其中41个病灶证实为复发微小肝癌,22个有病理结果,其余19个病灶经过随访证实.6个病灶为非肝癌病灶,全部由随访证实.所有病灶中,常规DSA诊断的灵敏度为73.2％,特异度为80.0％.DSA结合碘油CT诊断的灵敏度为90.2％,特异度为100％.Gd-EOB-DTPA增强MRI诊断的灵敏度为95.1％,特异度为100％.诊断效能之间统计学分析显示,常规DSA-DSA碘油CT以及常规DSA-MRI之间差异有统计学意义(P＜0.05),碘油CT与MRI间差异无统计学意义(P＞0.05).结论 对肝癌术后的微小肝癌结节,DSA联合碘油CT的诊断效能和Gd-EOB-DTPA增强MRI类似,对于临床上不适合做MRI的患者,可以考虑采用DSA联合碘油CT作为替代检查手段.     

Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties,clinical development and applications

Hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion represent a unique class of cell-specific MR contrast agents. Two hepatobiliary contrast agents, mangafodipir trisodium and gadobenate dimeglumine, are already clinically approved. A third hepatobiliary contrast agent, Gd-EOB-DTPA, is under consideration. The purpose of this review is to provide an overview on the properties, clinical development and application of these three hepatobiliary contrast agents. Bolus injectable paramagnetic hepatobiliary contrast agents combine established features of extracellular agents with the advantages of hepatocyte specificity. The detection and characterisation of focal liver disease appears to be improved compared to unenhanced MRI, MRI with unspecific contrast agents and contrast-enhanced CT. To decrease the total time spent by a patient in the MR scanner, it is advisable to administer the agent immediately after acquisition of unenhanced T1-w MRI. After infusion or bolus injection (with dynamic FS-T1-w 2D or 3D GRE) of the contrast agent, moderately and heavily T2w images are acquired. Post-contrast T1-w MRI is started upon completion of T2-w MRI for mangafodipir trisodium and Gd-EOB-DTPA as early as 20 min following injection, while gadobenate dimeglumine scans are obtained >60 min following injection. Post-contrast acquisition techniques with near isotropic 3D pulse sequences with fat saturation parallel the technical progress made by MSCT combined with an unparalleled improvement in tumour-liver contrast. The individual decision that hepatobiliary contrast agent one uses is partly based on personal preferences. No comparative studies have been conducted comparing the advantages or disadvantages of all three agents directly against each other.     

Enhancement characteristics of liver metastases, hepatocellular carcinomas, and hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging

Our objective was to study Gd-EOB-DTPA for the characterization of focal liver lesions by means of dynamic MR imaging. A double-blind and randomized dose-ranging phase-2 clinical trial was performed in 31 patients (liver metastases n = 23, hepatocellular carcinoma n = 4, and hemangioma n = 4) at a field strength of 1.0 Tesla. Gd-EOB-DTPA (Schering AG, Berlin, Germany) was administered as an IV bolus (12.5, 25, or 50 μmol/kg body weight) with dynamic T1-weighted MRI during the distribution and cellular uptake of the contrast agent at multiple time points up to 45 min post contrast. Dynamic changes in tumor signal intensity, tumor–liver contrast, enhancement patterns, side effects, and adverse events were evaluated. Monitoring of vital signs revealed no significant changes during bolus injection of Gd-EOB-DTPA. Liver metastases demonstrated an inhomogeneous uptake of Gd-EOB-DTPA during the distribution phase with a washout effect on delayed images > 3 min and highest tumor–liver contrast 20 and 45 min post contrast. Hepatocellular carcinomas showed prolonged enhancement as compared with metastases and hemangiomas. Hemangiomas exhibited an early peripheral–nodular enhancement with subsequent partial or complete filling, persisting enhancement < 10 min following injection of Gd-EOB-DTPA, and delayed washout as compared with liver metastases. Initial clinical experience suggests that Gd-EOB-DTPA as a bolus injectable hepatobiliary MR contrast agent may offer useful features for the characterization of focal liver lesions. Received 4 January 1996; Revision received 13 March 1996; Accepted 4 June 1996     

A multinuclear MR study of Gd-EOB-DTPA: Comprehensive preclinical characterization of an organ specific MRI contrast agent

The characterization of the hepatobiliary contrast agent Gd-EOB-DTPA (gadolinium 3, 6, 9-triaza-3, 6, 9-tris(carboxymethyl)-4-(4-ethoxybenzyl)-undecandicarboxylic acid) in various media (water solution, protein containing solution, phosphorylated metabolites solution, and excised and perfused liver) was performed using different NMR approaches: water ¹H nuclear magnetic relaxation dispersion profiles, ²H NMR longitudinal and transverse relaxation rates of labeled complex, water ¹⁷O transverse relaxation rates and chemical shifts, ³¹P relaxation rates and peak area of phosphorylated metabolites. The higher proton relaxivity of Gd-EOB-DTPA in water compared with Gd-DTPA is related to a shorter distance (r) between the water proton and the gadolinium ion and to a longer rotational correlation time (T_R) of the hydrated complex. Although the thermodynamic stability of Gd-EOB-DTPA is identical to the one of Gd-DTPA, its kinetic stability in solutions containing phosphorylated metabolites (ATP, phosphocreatine, and inorganic phosphate) as measured by ³¹P relaxation rates analysis is higher than for the parent compound. Gd-EOB-DTPA binds noncovalently to serum proteins. Its interaction with human serum albumin is characterized by a dissociation constant of 1-4.1 mM as calculated from proton and deuterium relaxation rates and equilibrium dialysis. This noncovalent interaction involves the subdomain IIA of human serum albumin. ³¹P spectroscopy of the excised and perfused rat livers was used to monitor the uptake of Gd-EOB-DTPA by the hepatocytes where it enhances the nuclear relaxation of the intracellular metabolites without impairing the adenosine triphosphate metabolism of the cells.     

钆塞酸二钠增强MRI在肝脏结节性病变中的诊断价值

目的探讨钆塞酸二钠增强MRI检查在肝脏结节性病变中的诊断价值。方法疑似为肝脏结节性病变的50例患者,所有患者依次行MRI平扫、钆塞酸二钠动态增强扫描及延迟肝细胞特异期扫描。结果 50例患者共发现局灶性结节73枚。病理或临床诊断肝细胞肝癌(HCC)25例、肝脏转移瘤7例,再生结节(RN)5例,退变结节(DN)6例,肝血管瘤6例,肝脏局灶性结节性增生(FNH)2例,肝腺瘤1例。钆塞酸二钠增强MRI共诊断HCC 24例,肝脏转移瘤7例,RN 5例,DN 6例,肝血管瘤6例,FNH 2例,肝腺瘤1例,总体符合率98.1%。钆塞酸二钠增强MRI动脉期、门脉期和平衡期所有病灶符合应用常规含钆(Gd)剂时的强化表现和特征,延迟20 min肝细胞特异期扫描时,大部分恶性结节呈现低信号,仅1例肝细胞肝癌呈稍高信号,大部分良性结节呈高信号,但肝血管瘤呈低信号。结论采用钆塞酸二钠行MRI动态增强扫描对肝脏结节性病变的诊断有较好的诊断价值,尤其是钆塞酸二钠动态增强扫描与肝细胞特异期扫描联合应用,可以提供病变形态、血供、细胞来源及功能等更多相关信息,从而提高诊断准确性。     

Gd-EOB-DTPA肝胆期MRI结合DWI对原发性肝细胞癌的检出价值

目的 在常规动态对比增强MRI的基础上,探讨Gd-EOB-DTPA增强MR扫描肝胆期结合扩散加权成像序列(DW-MRI)诊断原发性肝细胞癌的价值.方法 回顾性分析60例怀疑原发性肝细胞癌(hepatocellular carcinoma,HCC)患者的Gd-EOB-DTPA增强MR扫描动脉期、门脉期、肝胆期及DWI图像资料.分为3组进行阅读和比较,分析影像特征,获得最终影像诊断结果.以手术病理为标准,采用受试者工作特征曲线(ROC)曲线下面积(AUC)分析Gd-EOB-DTPA肝胆期结合DWI序列对HCC的诊断价值.结果 60例患者共发现肝内病灶80个,其中40例患者共诊断56个HCC,其中22个直径≤2 cm.在常规动态对比增强MR扫描基础上,结合Gd-EOB-DTPA肝胆期及DW-MRI不能增加对所有大小的HCC的诊断准确性,但对直径≤2 cm的早期HCC的准确性最高(P=0.024 8),且当仅结合Gd-EOB-DTPA增强MR扫描肝胆期时,其诊断准确性亦高于常规对比动态增强扫描(P =0.043 2),具统计学意义.结论 在常规动态对比增强MR基础上,结合Gd-EOB-DTPA增强肝胆期图像和DWI序列有助于诊断直径≤2 cm的早期HCC,可以作为常规MR序列的有效补充.     

MSCT和Gd-EOB-DTPA DCE-MRI诊断肝脏局灶性病变的价值对比

目的分析多排螺旋CT(MSCT)与钆塞酸二钠动态对比增强磁共振成像(Gd-EOB-DTPA DCE-MRI)对肝脏局灶性病变的诊断价值。方法回顾性分析我院68例经手术病理证实的肝脏局灶性病变患者临床资料。记录68例肝脏局灶性病变患者经手术病理检出的病灶情况,并比较MSCT与Gd-EOB-DTPA DCE-MRI对肝脏局灶性病变性质诊断价值差异。结果68例患者经手术病理共检出病灶228枚,其中恶性病灶182枚(79.82%),良性病灶46枚(20.18%)。MSCT对恶性病灶诊断准确170枚(93.41%),对良性病灶诊断准确36枚(78.26%),共诊断准确206枚(90.35%);Gd-EOB-DTPA DCE-MRI对恶性病灶诊断准确180枚(98.90%),对良性病灶诊断准确40枚(86.96%),共诊断准确220枚(96.49%)。2种检查方法对肝脏局灶性病变患者良恶性病灶诊断的特异度、阳性预测值比较,差异无统计学意义(P>0.05);但MSCT诊断的灵敏度、阴性预测值及准确率均低于Gd-EOB-DTPA DCE-MRI(P<0.05)。结论MSCT和Gd-EOB-DTPA DCE-MRI诊断肝脏局灶性病变均具有较高的诊断价值,但Gd-EOB-DTPA DCE-MRI诊断病灶性质的准确率更高,于临床诊治有利。     

普美显MRI增强扫描鉴别肝硬化结节与肝癌应用价值

选取本院2017～2018年的42例肝硬化患者行MRI增强扫描和普美显MRI增强扫描,将影像诊断与病理分析结果进行比较和探讨,发现MRI增强扫描和普美显MRI增强扫描的癌灶数量与病理诊断一致率分别为73.1%和96.2%,后者一致率更高(P<0.05)。此外,普美显MRI增强扫描对于诊断肝癌的灵敏度、特异性和准确度分别为94.1%、96.0%和97.6%,明显优于MRI增强扫描的诊断情况(P<0.05)。提示普美显MRI增强扫描可显著提高对肝硬化结节及肝癌的灵敏性、特异性和准确率,且能够将具有癌恶化趋势的肝硬化结节诊断出来,值得临床进一步研究和应用。     

Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging

AIM To assess the accuracy of Look-Locker on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(GdEOB-DTPA)-enhanced magnetic resonance imaging(MRI) for staging liver fibrosis in chronic hepatitis B/C(CHB/C).METHODS We prospectively included 109 patients with CHB or CHC who underwent a 3.0-Tesla MRI examination, including T1-weighted and Look-Locker sequences for T1 mapping. Hepatocyte fractions(He F) and relaxation time reduction rate(RE) were measured for staging liver fibrosis. A receiver operating characteristic analysis using the area under the receiver operating characteristic curve(AUC) was used to compare thediagnostic performance in predicting liver fibrosis between He F and RE.RESULTS A total of 73 patients had both pathological results and MRI information. The number of patients in each fibrosis stage was evaluated semiquantitatively according to the METAVIR scoring system: F0, n = 23(31.5%); F1, n = 19(26.0%); F2, n = 13(17.8%); F3, n = 6(8.2%), and F4, n = 12(16.4%). He F by EOB enhancement imaging was significantly correlated with fibrosis stage(r =-0.808, P 0.05). AUC values for diagnosis of any(≥ F1), significant(≥ F2) or advanced(≥ F3) fibrosis, and cirrhosis(F4) using He F were 0.837(0.733-0.913), 0.890(0.795-0.951), 0.957(0.881-0.990), and 0.957(0.882-0.991), respectively. He F measurement was more accurate than use of RE in establishing liver fibrosis staging, suggesting that calculation of He F is a superior noninvasive liver fibrosis staging method.CONCLUSION A T1 mapping-based He F method is an efficient diagnostic tool for the staging of liver fibrosis.