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.     

Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: on-site unblinded versus off-site blinded reading

Objective

To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions.

Materials and methods

99 patients (57 women and 42 men, age range 18–89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue^® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT.

Results

Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p < 0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p < 0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p < 0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ = 0.29–0.39) while it was good for CEUS (κ = 0.63–0.79).

Conclusions

CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.     

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.     

Impact of European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines on the use of contrast agents in liver ultrasound

The introduction of microbubble contrast agents and the development of contrast-specific techniques have opened new prospects in liver ultrasound. Over the past few years several reports have shown that contrast ultrasound can substantially improve detection and characterization of focal liver lesions with respect to baseline studies. The advent of second-generation agents and low mechanical index real-time scanning techniques has been instrumental in improving the easiness and the reproducibility of the examination. With the publication of the guidelines for the use of contrast agents in liver ultrasound by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), contrast ultrasound enters into clinical practice. The guidelines define the indications and recommendations for the use of contrast ultrasound in focal liver lesion detection, characterization, and follow-up after tumor ablation procedures. We discuss the impact of EFSUMB guidelines on diagnostic protocols currently adopted in liver imaging.     

Contrast agents for MR imaging of the liver

The evolution of contrast agents for MR imaging of the liver has proceeded along several different paths with the common goal of improving liver-lesion contrast. These contrast agents are used to accentuate the inherent differences in liver-lesion signal intensity through differential enhancement of proton relaxation within adjacent tissues. Contrast agents used for hepatic MR imaging can be broadly categorized into those that target the extracellular space, the hepatobiliary system, and the reticuloendothelial system. Although only a small number of liver contrast agents are currently available, others are rapidly proceeding through clinical trials and may soon be added to our clinical armamentarium. This article will briefly review the current clinical experience with these agents, discussing their mechanism of contrast enhancement, pharmacokinetics, and efficacy in the evaluation of focal liver lesions.     

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.     

Role of contrast enhanced ultrasound in characterization of focal liver lesions

Aim

The purpose of the study was to describe the enhancement patterns of focal liver lesions (FLLs) on contrast enhanced sonography (CEUS), assessing the potential of this technique for characterizing the lesions and to compare its diagnostic accuracy with conventional baseline sonography including color Doppler.

Materials and methods

Between August 2009 and July 2010, 50 patients with FLLs underwent gray scale sonography, color Doppler and CEUS. The enhancement patterns of these FLL’s were analyzed throughout the arterial phase, the portal venous phase and the extended portal venous phase (the late parenchymal phase). The final diagnosis was established on the basis of histopathologic examination or CT/MRI imaging.

Results

Out of these 50 FLLs, 33 were malignant (4 hepatocellular carcinoma and 29 metastasis) and 17 were benign (5 hemangioma, 5 abscess, 2 cyst and 1 each of FNH, focal fat sparing area, focal fatty infiltration, adenoma and benign/granulomatous lesion). The enhancement patterns after injecting microbubble contrast agent allowed characterization of FLLs. The malignant lesions showed intratumoral and/or peritumoral vascularity during the arterial phase and perfusion defect during the late parenchymal phase. Contrast enhanced sonography improved sensitivity in detecting malignancy (CEUS vs. baseline sonography, 100% vs. 81.8%).

Conclusion

CEUS improves detection and characterization of FLLs. It should be used as problem solving tool in cases where conventional gray scale and color Doppler sonography are non-diagnostic.     

Comparison of liver perfusion parameters studied with conventional extravascular and experimental intravascular CT contrast agents

RATIONALE AND OBJECTIVES: To compare liver perfusion parameters obtained by using an extravascular contrast agent and a blood-pool agent. MATERIALS AND METHODS: Fifteen rabbits were imaged with a continuous 40-second single-slice computed tomography acquisition after a bolus injection of contrast agent (physiologic bolus duration 4-5 seconds, extravascular iohexol, n = 7; experimental nanoparticulated blood-pool agent WIN8883, n = 8). Time-density curves were generated for the aorta, portal vein, and liver. From the curves, arterial, portal, and total blood flows and hepatic perfusion index (HPI, arterial-to-total perfusion ratio) were determined by using two commonly applied fundamentally different analyzing methods: the single-compartment model and the peak gradient (PG) method. Also, the gamma variate fitting method was used. RESULTS: By using the single-compartment model, the obtained HPI and total blood flow were 0.14 +/- 0.04 and 2.29 +/- 0.40 (mL/min/mL(tissue)) for WIN8883, and 0.15 +/- 0.06 (P = .54) and 4.60 +/- 1.14 (mL/min/mL(tissue)) (P = .0002) for iohexol, respectively. With the PG, HPI and total blood flow were 0.15 +/- 0.08 and 1.27 +/- 0.24 (mL/min/mL(tissue)) for WIN8883, and 0.20 +/- 0.06 (P = .12) and 2.11 +/- 0.25 (mL/min/mL(tissue)) (P = .00002) for iohexol, respectively. With the blood pool agent, similar contrast enhancement to the conventional agent was achieved with about 36% reduced dosage of iodine per body weight (mg I/kg). CONCLUSIONS: HPI was found to be quite insensitive to different contrast agent types and analyzing methods. However, the arterial, portal and total liver blood flow values strongly depend on contrast agent type and modeling method.     

Assessment of reperfusion injury by means of MR contrast agents in rat liver

The purpose of this study was to investigate whether extracellular MR contrast agents or intracellular liver-specific MR contrast agents may enable the assessment of liver reperfusion injury. Ischemia-related reperfusion was induced in 32 rats using Pringle's maneuver. Pringle's maneuver consisted of cross-clamping of the complete hepatoduodenal ligament for 45 minutes followed by 90 minutes of reperfusion. Two extracellular (gadopentetate dimeglumine and gadobutrol) and two intracellular (gadoxetic acid and SH U 555 A) MR contrast agents were evaluated as model agents. Control animals and animals with liver ischemia were used to calculate changes in liver signal enhancement after Pringle's maneuver. Significant changes in liver signal after reperfusion injury were observed only with reticuloendothelial system (RES)-specific SH U 555 A. Liver signal enhancement after Pringle's maneuver with RES-specific SH U 555 A was decreased by 25.4% as compared with the control group. RES-specific contrast agents such as SH U 555 A seem to be more sensitive to ischemia-related dysfunction of the liver than hepatobiliary contrast agents such as gadoxetic acid or extracellular gadolinium chelates at different concentrations because Kupffer cells are more sensitive to liver ischemia than hepatocytes.     

Hepatocellular MR contrast agents: enhancement characteristics of liver parenchyma and portal vein after administration of gadoxetic acid in comparison to gadobenate dimeglumine

Purpose

To investigate the enhancement characteristics of liver parenchyma and portal vein as well as the portal vein-to liver contrast in Gd-EOB-DTPA- and Gd-BOPTA-enhanced abdominal MRI.

Materials and methods

The local institutional review board approved this retrospective study. A total of 70 patients (30 female, 40 male) without relevant liver disease underwent either Gd-EOB-DTPA-enhanced (35 patients, dose 0.025 mmol/kg) or Gd-BOPTA-enhanced (35 patients, dose 0.1 mmol/kg) abdominal MRI. Signal-to-noise ratios (SNR) for the portal vein and the liver as well as portal vein-to-liver contrast-to-noise ratios (CNR) were calculated for three consecutive arterial phases, one portal venous phase and one delayed imaging phase.

Results

The liver SNR showed higher values for the Gd-BOPTA group in the arterial and portal venous phases (statistically significant for the second and third arterial phase), while the liver SNR in the delayed phase was higher for the Gd-EOB-DTPA group. The portal venous SNR as well as the portal vein-to-liver CNR was higher in the Gd-BOPTA group in all imaging phases (statistically significant in all phases except for the first arterial phase).

Conclusion

The enhancement of liver parenchyma and portal vein as well as the portal vein-to-liver contrast in the arterial and portal venous imaging phases were higher for patients receiving Gd-BOPTA compared with Gd-EOB-DTPA at the respective recommended doses. Gd-BOPTA might therefore enable better evaluation of the portal vein.     

MR imaging contrast agents — what's in a name?

The purpose of this brief review is to reduce the confusion surrounding the nomenclature of MRI contrast agents. There are several different categories of contrast agents for potential use in human diagnosis and several alternative names for each contrast agent, an array of choices that actually changes over time. This review describes the general process by which these various agents are named, presents one general categorization by which these agents can be considered, and provides a concise table to which readers can refer to identify the proper name to use for each of the agents that has thus far been administered to humans.     

Tumor characterization with dynamic contrast–enhanced MRI using mr contrast agents of various molecular weights

Dynamic contrast-enhanced MR imaging was used to measure the kinetics of enhancement in three different animal tumor models (Walker 256, R3230 AC, MCF7) using three different Gd complexes (Gd-DTPA, Gd-DTPA-24-cascade-poly-mer 30 kD, and polylysine-Gd-DTPA 50 kD). The three tumor models varied in growth rate, with the most rapid growth demonstrated by Walker 256 cells and the slowest growth occurring in the MCF7 cells. For each tumor, the kinetics of enhancement using polylysine-Gd-DTPA was analyzed using a pharmacokinetic model to estimate the vascular volume of the tumor. The rate of entry of the contrast agent into the interstitial space served as the measure of vascular permeability. The smallest molecular-weight agent, Gd-DTPA, could not provide information about vascular permeability. The intermediate and the largest agents both demonstrated that the faster-growing Walker 256 tumor had greater vascular permeability than did the slower-growing R3230 AC tumor. The degree of vascular permeability in the MCF7 tumor could not be assessed fairly due to insufficient statistics. The current study provides evidence supporting the hypothesis that more rapidly growing tumors have higher vascular permeability than do tumors that grow more slowly.     

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.     

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.     

The value of gadoterate meglumine as a gastrointestinal contrast agent in MRI

To evaluate the safety and efficacy of a gadoterate meglumine formulation as an oral contrast agent, MRI (0.5 T) was performed on 29 patients with abdominal disease before and after administration of contrast material. The patients ingested 16 ml/kg of a gadoterate meglumine solution (10 g/l glucose, 2 mmol/l gadoterate meglumine) over 1 h. Fourteen per cent of patients had mild side effects related to the contrast agent. Significant hyperintense contrast enhancement was achieved for the stomach and duodenum allowing better delineation of gastric and duodenal walls, entire pancreas and spleen on T1- and T2-weighted spin echo sequences. In 5 patients more diagnostic information was available from post-contrast images compared with precontrast images. This study shows that gadoterate meglumine is a safe and well-tolerated contrast agent that improves MRI of the proximal gastrointestinal tract and upper abdomen.Presented at the European Congress of Radiology, Vienna, Austria, 15–20 September 1991 Correspondence to: Y. Miaux     

经量化的扩散加权成像对肝脏占位性病变的鉴别诊断价值

目的：探讨经量化的扩散加权成像(DWI)在肝脏占位性疾病影像诊断中的价值。方法本组回顾性分析120例肝脏占位性病变患者及对照组12例正常肝脏的影像资料,应用3.0T MR 行常规 MR 及 DWI,120例患者共检出179个病灶(其中53个肝癌、61个转移瘤、32个肝血管瘤及33个肝囊肿),分析其与对照组的 DWI 图及表观扩散系数(ADC)图,并测量 ADC 值,比较其间是否存在统计学差异。结果本组研究 b 值选择800 s/mm2,(1)其中33个肝囊肿呈低信号,51个肝癌、61个肝转移瘤及32个肝血管瘤呈高信号,肝囊肿的 DWI 图像信号与肝癌、肝转移瘤及肝血管瘤有显著性差异(P <0.05);(2)肝癌、肝转移瘤 ADC 伪彩图大体呈冷色系表现,肝囊肿、肝血管瘤 ADC 伪彩图大体呈暖色系表现;(3)肝癌、肝转移瘤、肝血管瘤、肝囊肿平均 ADC 值相互间行两两比较,总体上存在统计学差异(P <0.05),但肝癌与肝转移瘤之间两两比较,无统计学差异(P >0.05),通过结合背景肝,比较肝癌的病灶/背景肝 ADC 值与肝转移瘤的病灶/背景肝 ADC 值,二者差异有显著性(P <0.05)。结论DWI 和 ADC 图分析及ADC 值测量可为肝脏占位性病的诊断及鉴别诊断提供重要的补充信息。     

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。     

Nonspecificity of the fat-sparing ring surrounding focal liver lesion at MR imaging

RATIONALE AND OBJECTIVES: The presence of a fat-sparing ring surrounding focal liver lesions in patients with steatosis has been described only in malignant lesions. Our purpose is to evaluate whether this fat-sparing ring peripheral to tumors is a specific marker of malignancy. MATERIALS AND METHODS: From 300 magnetic resonance examinations of focal liver lesions, 132 patients with a confirmed nature of the lesions were selected. There were 24 patients (18.2%) with lesions having a perilesional fat-sparing ring in the opposed-phase spoiled T1-weighted gradient echo images. All these livers had steatosis. RESULTS: Perilesional fat-sparing rings were observed in 19 (21.6%) malignant and 5 (11.4%) benign lesions. Size of the lesion was not related to the presence of the fat-sparing ring (P=.6), neither was type of lesion (malignant versus benign) statistically related to the presence of the perilesional fat-sparing ring in the opposed-phase gradient echo magnetic resonance images (chi-square, P=.15). Fat-sparing rings were mainly seen in metastases (51.4% of metastases), but seldom in primary malignant tumors (1.9% of hepatocellular carcinomas). Hemangiomas also presented this finding (18.5% of hemangiomas). CONCLUSIONS: We believe that the presence of this bright rim surrounding lesions on oppose-phase images in patients with steatosis mainly represent decrease portal flow, either because of compressed and atrophic hepatocyte cords with sinusoidal congestion in expanding metastatic lesions or the presence of arterioportal perfusion abnormalities in vascularized hemangiomas.     

Delineation of liver necrosis using double contrast-enhanced MRI

The purpose of this study was to demonstrate the potential usefulness of the combination of gadolinium and dysprosium to enhance the difference between normal and necrotic liver tissue. Small regions of acute necrosis were induced by injecting 200–300 μl of 95% alcohol into the liver of 26 rats. MRI was performed 24 hours after necrosis induction, before and immediately after injection of one or both contrast agents. Using a mixed T1/T2-weighted sequence, the signal intensity (SI) of the normal liver was reduced by 70%, whereas the necrotic regions had more than a 50% increase in SI after double contrast. The region that was enhanced corresponded largely with the region of necrosis as observed postmortem. The lesion size, when identified, was largely underestimated using either of the agents alone, albeit using the common pulse sequences. The double contrast effect of simultaneous administration of gadolinium and dysprosium allows accurate delineation of liver necrosis.     

Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

Although the diagnostic application of echoplanar imaging (EPI) has until now been limited, recent technical advances provide anatomic resolution and signal-to-noise ratios comparable to that of conventional MR imaging. The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flash images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. Approved aqueous gastrointestinal contrast media or flavored saline with long relaxation times may serve as safe, simple, and effective gastrointestinal contrast agents in abdominal EPI. Correspondence to: P. Reimer