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Focal liver lesions detection and characterization: The advantages of gadoxetic acid-enhanced liver MRI
Abstract
Since its clinical introduction, several studies in literature have investigated gadolinium ethoxybenzhyl diethylenetriaminepentaacetic acid or gadoxetic acid (Gd-EOB-DTPA) properties. Following contrast injection, it provides dynamic vascular phases (arterial, portal and equilibrium phases) and hepatobiliary phase, the latter due to its uptake by functional hepatocytes. The main advantages of Gd-EOB-DTPA of focal liver lesion detection and characterization are discussed in this paper. Namely, we focus on the possibility of distinguishing focal nodular hyperplasia (FNH) from hepatic adenoma (HA), the identification of early hepatocellular carcinoma (HCC) and the pre-operative assessment of metastasis in liver parenchyma. Regarding the differentiation between FNH and HA, adenoma typically appears hypointense in hepatobiliary phase, whereas FNH is isointense or hyperintense to the surrounding hepatic parenchyma. As for the identification of early HCCs, many papers recently published in literature have emphasized the contribution of hepatobiliary phase in the characterization of nodules without a typical hallmark of HCC. Atypical nodules (no hypervascularizaton observed on arterial phase and/or no hypovascular appearance on portal phase) with low signal intensity in the hepatobiliary phase, have a high probability of malignancy. Finally, regarding the evaluation of focal hepatic metastases, magnetic resonance pre-operative assessment using gadoxetic acid allows for more accurate diagnosis.
... Kontrast öncesi sekanslardaki spesifik veya yönlendirici olabilecek ip uçlarına ek olarak kontrast sonrası sekanslardaki lezyonun geç arteryel fazdaki morfolojik kontrastlanma paterni ve geç portal venöz fazdaki temporal kontrastlanma paterni ayırıcı tanıda yardımcı olmaktadır. Ayrıca zaman içerisinde geliştirilen karaciğer spesifik kontrast maddeleri [10][11][12][13][14] ve son yıllarda yaygın olarak kullanıma giren difüzyon ağırlıklı görüntüler (DAG) [3,7,15] lezyonların tespiti ve ayrıcı tanısındaki sensitivite ve spesifiteyi arttırmıştır. ...
... MRG, özellikle küçük boyuttaki (≤1 cm) karaciğer metastazlarının saptanmasında ve karakterize edilmesinde sensitivitesi ve spesifitesi en yüksek metod olarak kabul edilmektedir [4,6,7]. Hepatobiliyer kontrast maddeler ve DAG özellikle küçük boyuttaki bu metastazların saptanmasında sensitiviteyi arttırmaktadır [12][13][14][15]. Günümüzde Gadobenat dimeglumin (Gd-BOPTA; Multi-Hance, Bracco Imaging, Milan, Italy) ve Gadoxetik asid (Gd-EOB; Primovist, Bayer Schering Pharma AG, Berlin Germany) olmak üzere iki farklı hepatobiliyer paramagnetik gadolinyum şelatı kontrast madde bulunmaktadır. ...
... iken Gd-BOPTA'dan sonra 1-2 saat kadardır. Ancak Gd-BOPTA daha yüksek relaksiviteye sahiptir [9][10][11][12][13][14]. Hepatobiliyer fazda sağlıklı karaciğer belirgin kontrast tutarak hiperintens, hem hipovasküler hem de hipervasküler metastazlar ise fonksiyone hepatosit veya safra yolu içermediğinden kontrast tutulumu göstermeyerek hipointens izlenmektedir. ...
... Contrast-enhanced magnetic resonance imaging (MRI) scanning has been shown to be the most sensitive modality for the characterization of FNH and is increasingly applied [10][11][12][13][14][15]. However, characterization might still be challenging, e.g. for single lesions being too small to characterize (TSTC lesions) or in patients with a history of cancer [13][14][15][16][17][18]. Furthermore, the differential diagnosis can be difficult in cases of atypical appearance (e.g. ...
... Furthermore, the differential diagnosis can be difficult in cases of atypical appearance (e.g. missing central scar) or in elderly patients with underlying chronic liver disease at risk for hepatocellular carcinoma (HCC) [16][17][18]. Invasive diagnostics, e.g. percutaneous biopsy of hypervascular lesions might be associated with bleeding and tumor spread in case of malignancy. ...
... There is an emerging interest in managing incidental findings in the liver and pancreas [3-5, 7-9, 37]. Among cross-sectional imaging, MRI is considered the most reliable imaging method for classifying incidental liver lesions, especially after recent improvements, e.g. the introduction of the new T1-positive liver specific contrast agent, gadoxetic acid (Gd-EOB-DTPA, Primovist or Evosit, Bayer Schering Pharma, Germany) [13][14][15][16][17][18]. However, even after combining different non-invasive imaging modalities, e.g. ...
Focal nodular hyperplasia (FNH) are benign lesions in the liver. Although liver resection is generally not indicated in these patients, rare indications for surgical approaches indeed exist. We here report on our single-center experience with patients undergoing liver resection for FNH, focussing on preoperative diagnostic algorithms and quality of life (QoL) after surgery.
Medical records of 100 consecutive patients undergoing liver resection for FNH between 1992 and 2012 were retrospectively analyzed with regard to diagnostic pathways and indications for surgery. Quality of life (QoL) before and after surgery was evaluated using validated assessment tools. Student’s t test, one-way ANOVA, χ 2 , and binary logistic regression analyses such as Wilcoxon–Mann–Whitney test were used, as indicated.
A combination of at least two preoperative diagnostic imaging approaches was applied in 99 cases, of which 70 patients were subjected to further imaging or tumor biopsy. In most patients, there was more than one indication for liver resection, including tumor-associated symptoms with abdominal discomfort (n = 46, 40.7 %), balance of risk for malignancy/history of cancer (n = 54, 47.8 %/n = 18; 33.3 %), tumor enlargement/jaundice of vascular and biliary structures (n = 13, 11.5 %), such as incidental findings during elective operation (n = 1, 0.9 %). Postoperative morbidity was 19 %, with serious complications (>grade 2, Clavien–Dindo classification) being evident in 8 %. Perioperative mortality was 0 %. Liver resection was associated with a significant overall improvement in general health (very good–excellent: preoperatively 47.4 % vs. postoperatively 68.1 %; p = 0.015).
Liver resection remains a valuable therapeutic option in the treatment of either symptomatic FNH or if malignancy cannot finally be ruled out. If clinically indicated, liver resection for FNH represents a safe approach and may lead to significant improvements of QoL especially in symptomatic patients.
... Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a hepatocyte-specific MRI contrast agent. [23] It acts as an extracellular contrast agent in the early phase after intravenous injection, and it is subsequently taken up by the hepatocytes. It enhances the detection and diagnosis of hepatocellular carcinoma and is considered a functional contrast medium. ...
... [42] Gd-EOB-DTPA is a liver-specific MRI contrast agent, and the indices obtained from contrast images assess both liver function and fibrosis. [23,46,47] The significant decrease in the contrast index with advanced-fibrosis compared with mild-fibrosis is due to the reduced uptake of disodium gadoxetate by hepatocytes as a result of reduced normal hepatocyte numbers caused by fibrotic tissue growth or severe hepatocellular dysfunction, degeneration, and necrosis. [48,49] The accumulation of Gd-EOB-DTPA in the liver is associated with several other factors, including individual indocyanine green clearance and plasma bilirubin levels. ...
Preoperative assessment of the degree of liver fibrosis is important to determine treatment strategies. In this study, galactosyl human serum albumin single-photon emission-computed tomography and ethoxybenzyl (EOB) contrast-enhanced magnetic resonance imaging (MRI) were used to assess the changes in hepatocyte function after liver fibrosis, and the standardized uptake value (SUV) was combined with gadolinium EOB-diethylenetriaminepentaacetic acid to evaluate its added value for liver fibrosis staging.
A total of 484 patients diagnosed with hepatocellular carcinoma who underwent liver resection between January 2010 and August 2018 were included. Resected liver specimens were classified based on pathological findings into nonfibrotic and fibrotic groups (stratified according to the Ludwig scale). Galactosyl human serum albumin-single-photon emission-computed tomography and EOB contrast-enhanced MRI examinations were performed, and the mean SUVs (SUVmean) and contrast enhancement indices (CEIs) were obtained. The diagnostic value of the acquired SUV and CEIs for fibrosis was assessed by calculating the area under the receiver operating characteristic curve (AUC).
In the receiver operating characteristic analysis, SUV + CEI showed the highest AUC in both fibrosis groups. In particular, in the comparison between fibrosis groups, SUV + CEI showed significantly higher AUCs than SUV and CEI alone in discriminating between fibrosis (F3 and 4) and no or mild fibrosis (F0 and 2) (AUC: 0.879, vs SUV [P = 0.008], vs. CEI [P = 0.023]), suggesting that the combination of SUV + CEI has greater diagnostic performance than the individual indices.
Combining the SUV and CEI provides high accuracy for grading liver fibrosis, especially in differentiating between grades F0 and 2 and F3–4. SUV and gadolinium EOB-diethylenetriaminepentaacetic acid-enhanced MRI can be noninvasive diagnostic methods to guide the selection of clinical treatment options for patients with liver diseases.
... Specifically, this approach can differentiate LGDNs from premalignant HGDNs and early HCC [37] . The hypointense appearance in hepatobiliary phase is often considered a radiological marker of nodule differentiation [38] . The Gd-EOB-DTPA-enhanced MRI findings of nodules (LGDNs, HGDNs, and HCCs), which were histologically identified on cirrhotic and explanted livers, indicated nodular hypointensity at the hepatobiliary (HB) phase in 39/40 HCCs and 21/30 HGDNs but in none of the LGDNs, despite a lack of significant differences among the enhancement ratios (ERs) of HGDNs and HCCs at the HB phase [39] . ...
... In one study, 62 of 215 nodules exhibited atypical radiological behavior (atypical nodules refer to a lack of hypervascularization in the arterial phase and/or absent hypovasculature in portal phase [38] ), and 19 out of 20 HGDNs/early HCC nodules were found to be hypointense in the HB phase [41] . Most HGDNs (20/30) were reported to be iso/hypointense in the arterial phase and hypointense in the late phase, where all ...
Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma (HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.
... 3,4 Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; gadoxetic acid disodium; Primovist, Bayer Schering Pharma, Berlin, Germany) is a liver-specific contract agent for MRI imaging. 5 Approximately 50% of injected GD-EOB-DTPA is taken up by functioning hepatocytes and excreted in the bile, thus enabling hepatobiliary phase imaging to begin approximately 10 to 20 minutes after injection. 4,5 Studies have shown that GD-EOB-DTPA MRI provides excellent diagnostic accuracy for both HCC 6 and incidental lesions in the liver. ...
... 5 Approximately 50% of injected GD-EOB-DTPA is taken up by functioning hepatocytes and excreted in the bile, thus enabling hepatobiliary phase imaging to begin approximately 10 to 20 minutes after injection. 4,5 Studies have shown that GD-EOB-DTPA MRI provides excellent diagnostic accuracy for both HCC 6 and incidental lesions in the liver. 7 Some even suggested that GD-EOB-DTPA-enhanced MRI may replace CT arterial portography (CTAP) and CT hepatic arteriography (CTHA). ...
The purpose of this meta-analysis was to compare the diagnostic accuracy of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and multidetector-row computed tomography (MDCT) for hepatocellular carcinoma (HCC).
Medline, Cochrane, EMBASE, and Google Scholar databases were searched until July 4, 2014, using combinations of the following terms: gadoxetic acid disodium, Gd-EOB-DTPA, multidetector CT, contrast-enhanced computed tomography, and magnetic resonance imaging. Inclusion criteria were as follows: confirmed diagnosis of primary HCC by histopathological examination of a biopsy specimen; comparative study of MRI using Gd-EOB-DTPA and MDCT for diagnosis of HCC; and studies that provided quantitative outcome data. The pooled sensitivity and specificity of the 2 methods were compared, and diagnostic accuracy was assessed with alternative-free response receiver-operating characteristic analysis.
Nine studies were included in the meta-analysis, and a total of 1439 lesions were examined. The pooled sensitivity and specificity for 1.5T MRI were 0.95 and 0.96, respectively, for 3.0T MRI were 0.91 and 0.96, respectively, and for MDCT were 0.74 and 0.93, respectively. The pooled diagnostic odds ratio for 1.5T and 3.0T MRI was 242.96, respectively, and that of MDCT was 33.47. To summarize, Gd-EOB-DTPA-enhanced MRI (1.5T and 3.0T) has better diagnostic accuracy for HCC than MDCT.
... Gadoxetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) is increasingly applied for several indications, including detection of premalignant and secondary liver lesions, characterization of liver lesions, and assessment of liver (dys)function [1,2]. Clinically relevant primary liver lesions include focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), and hepatocellular carcinoma (HCC) [3]. ...
Objectives
Hyper- or isointensity in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI has high specificity for focal nodular hyperplasia (FNH) but may be present in hepatocellular adenoma and carcinoma (HCA/HCC). This study aimed to identify imaging characteristics differentiating FNH and HCA/HCC.
Materials and methods
This multicenter retrospective cohort study included patients with pathology-proven FNH or HCA/HCC, hyper-/isointense in the HBP of gadoxetic acid-enhanced MRI between 2010 and 2020. Diagnostic performance of imaging characteristics for the differentiation between FNH and HCA/HCC were reported. Univariable analyses, multivariable logistic regression analyses, and classification and regression tree (CART) analyses were conducted. Sensitivity analyses evaluated imaging characteristics of B-catenin-activated HCA.
Results
In total, 124 patients (mean age 40 years, standard deviation 10 years, 108 female) with 128 hyper-/isointense lesions were included. Pathology diagnoses were FNH and HCA/HCC in 64 lesions (50%) and HCA/HCC in 64 lesions (50%). Imaging characteristics observed exclusively in HCA/HCC were raster and atoll fingerprint patterns in the HBP, sinusoidal dilatation on T2-w, hemosiderin, T1-w in-phase hyperintensity, venous washout, and nodule-in-nodule partification in the HBP and T2-w. Multivariable logistic regression and CART additionally found a T2-w scar indicating FNH, less than 50% fat, and a spherical contour indicating HCA/HCC. In our selected cohort, 14/48 (29%) of HCA were B-catenin activated, most (13/14) showed extensive hyper-/isointensity, and some had a T2-w scar (4/14, 29%).
Conclusion
If the aforementioned characteristics typical for HCA/HCC are encountered in lesions extensively hyper- to isointense, further investigation may be warranted to exclude B-catenin-activated HCA.
Clinical relevance
Hyper- or isointensity in the HBP of gadoxetic acid-enhanced MRI is specific for FNH, but HCA/HCC can also exhibit this feature. Therefore, we described imaging patterns to differentiate these entities.
Key Points
FNH and HCA/HCC have similar HBP intensities but have different malignant potentials .
Six imaging patterns exclusive to HCA/HCC were identified in this lesion population .
These features in liver lesions hyper- to isointense in the HBP warrant further evaluation .
... Recently, one of the contrast agents introduced in clinical practice is gadoxetic acid (gadoxetate), formed by gadolinium and the ligand ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) [2]. The gadoxetic acid has hepatocellular uptake and biliary excretion (about 50% in healthy patients), which allows to carry out routine three-phase dynamic studies at first (arterial, portal and transitional/ equilibrium), with the characteristics of the liver parenchyma and FLL similar to the extracellular gadolinium, such as gadopentetate dimeglumine (Gd-DTPA), followed by hepatobiliary assessment in the same exam [3][4][5][6]. Given the particular importance in each patient's outcome of the correct diagnosis of a challenging focal liver lesion, the recent introduction of this contrast medium in MRI and its potential uses, the objective was to determine the value of hepatobiliary phases (HBP) using gadoxetic acid as a liver-specific agent in MRI in addition to the non-contrast and dynamic phases after contrast in the characterization of benign and malignant FLL in clinical practice, including hepatocellular carcinoma (HCC) and metastases. ...
Background:
Challenging lesions, difficult to diagnose through non-invasive methods, constitute an important emotional burden for each patient regarding a still uncertain diagnosis (malignant x benign). In addition, from a therapeutic and prognostic point of view, delay in a definitive diagnosis can lead to worse outcomes. One of the main innovative trends currently is the use of molecular and functional methods to diagnosis. Numerous liver-specific contrast agents have been developed and studied in recent years to improve the performance of liver magnetic resonance imaging (MRI). More recently, one of the contrast agents introduced in clinical practice is gadoxetic acid (gadoxetate disodium).
Aim:
To demonstrate the value of the hepatobiliary phases using gadoxetic acid in MRI for the characterization of focal liver lesions (FLL) in clinical practice.
Methods:
Overall, 302 Lesions were studied in 136 patients who underwent MRI exams using gadoxetic acid for the assessment of FLL. Two radiologists independently reviewed the MRI exams using four stages, and categorized them on a 6-point scale, from 0 (lesion not detected) to 5 (definitely malignant). The stages were: stage 1- images without contrast, stage 2- addition of dynamic phases after contrast (analogous to usual extracellular contrasts), stage 3- addition of hepatobiliary phase after 10 min (HBP 10'), stage 4- hepatobiliary phase after 20 min (HBP 20') in addition to stage 2.
Results:
The interobserver agreement was high (weighted Kappa coefficient: 0.81- 1) at all stages in the characterization of benign and malignant FLL. The diagnostic weighted accuracy (Az) was 0.80 in stage 1 and was increased to 0.90 in stage 2. Addition of the hepatobiliary phase increased Az to 0.98 in stage 3, which was also 0.98 in stage 4.
Conclusion:
The hepatobiliary sequences improve diagnostic accuracy. With growing potential in the era of precision medicine, the improvement and dissemination of the method among medical specialties can bring benefits in the management of patients with FLL that are difficult to diagnose.
... Considering the smaller administered volume and lower gadolinium content of gadoxetate disodium-enhanced MRI in comparison with extracellular contrast-enhanced MRI [15], the weak arterial hyperenhancement with gadoxetate disodium could cause a relatively low visualization score. By contrast, we found that HBP had the highest visualization score, a finding similar to previous studies that reported improved detection and localization of focal hepatic observations, including HCC, using gadoxetate disodium-enhanced MRI [16][17][18] (e.g., the sensitivity for hypovascular HCC was significantly increased from 59 to 95% using HBP imaging with gadoxetate disodium-enhanced MRI [19]). This good performance can be explained by high lesion-to-liver contrast and high conspicuity during the HBP of gadoxetate disodium-enhanced MRI [20,21]. ...
PurposeWe aimed to determine the optimal image sequence for measurement of hepatic observations on gadoxetate disodium-enhanced MRI in comparison with pathologic measurement, and to evaluate its clinical impact on the Liver Imaging Reporting and Data System (LI-RADS) v2018 classification.Methods
Two hundred and fifty-three patients (279 hepatic observations) who underwent gadoxetate disodium-enhanced MRI and subsequent hepatectomy were retrospectively included. Two radiologists independently evaluated the visualization score (five-point scale) and size of each observation on six MRI sequences (T1-weighted, T2-weighted, arterial-phase, portal venous-phase, transitional-phase [TP], and hepatobiliary-phase [HBP] images) and assigned a LI-RADS category. Correlations between MRI and pathologic measurements were evaluated using Pearson correlation coefficients. A repeated measures analysis of variance with Bonferroni post hoc comparison tests was used to compare the visualization scores and absolute differences between MRI sequences and pathologic measurements. The LI-RADS classification according the size measurement of each MRI sequence was compared using Cochran’s Q test with a post hoc McNemar’s test.ResultsOf the MRI sequences, HBP had the highest visualization score (4.1 ± 0.6) and correlation coefficient (r = 0.965). The absolute difference between MRI and pathologic measurement was lowest on TP (2.3 mm ± 2.2), followed by HBP (2.4 mm ± 2.1). In the LI-RADS classifications, HBP did not have any non-visible observations. Regarding LR-3, LR-4, and LR-5, there was no significantly different LI-RADS classification among the six MRI sequences (p ≥ 0.122).Conclusion
Hepatobiliary-phase images are clinically useful for measuring hepatic observations on gadoxetate disodium-enhanced MRI, especially regarding visibility and correlation with pathologic findings.
... Then, this is excreted into the biliary tract through multidrug resistance-associated protein 2 (MRP2) on the biliary tract of the liver membrane. The period of this phase is called the hepatobiliary specific period or hepatobiliary phase [19,20]. The remaining contrast agent, similar to Gd-DTPA, can be excreted through the kidney. ...
Background:
Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, and its morbidity and mortality have been increasing in recent years. The early diagnosis and prompt treatment of small HCC are crucial to improve the prognosis and quality of life of patients. In China, hepatitis B virus infection is the main cause. HCC with a single tumor nodule of ≤ 3 cm in diameter, or HCC with a number of nodules, in which each nodule is ≤ 2 cm in diameter, with a total diameter of ≤ 3 cm, is considered as small HCC. The MRI liver-specific contrast agent can detect small HCC at the early stage. This has important clinical implications for improving the survival rate of patients.
Main body:
Gd-EOB-DTPA-enhanced MRI can significantly improve the sensitivity and specificity of the detection of HBV-related small hepatocellular carcinoma, providing an important basis for the clinical selection of appropriate personalized treatment. Gd-EOB-DTPA-enhanced MRI can reflect the degree of HCC differentiation, and the evaluation of HCC on Gd-EOB-DTPA-enhanced MRI would be helpful for the selection of the treatment and prognosis of HCC patients. The present study reviews the progress of the application of Gd-EOB-DTPA in the early diagnosis of small HCC, its clinical treatment, the prediction of the degree of differentiation, and the assessment of recurrence and prognosis of HCC, including the pharmacoeconomics and application limitations of Gd-EOB-DTPA. The value of the application of HCC with the Gd-EOB-DTPA was summarized to provide information for improving the quality of life and prolonging the survival of patients.
Conclusion:
Gd-EOB-DTPA-enhanced MRI has the diagnostic capability for small HCC with a diameter of ≤ 2 cm. This will have a broader application prospect in the early diagnosis of small liver cancer with a diameter of ≤ 1 cm in the future. The relationship between GD-EOB-DTPA-MRI and the degree of HCC differentiation has a large research space, and Gd-EOB-DTPA is expected to become a potential tool for the preoperative prediction and postoperative evaluation of HCC, which would be beneficial for more appropriate treatments for HCC patients.
... For instance, by increasing the flip angle the contrast between normal liver parenchyma with gadoxetic acid uptake and excretion is effectively increased. These effects are mainly due to the different pharmacokinetic properties of the Gadoxetic Acid involving in the liver, a multidrug resistance-associated proteins complex (MRPs) able to excrete an half of the contrast media by the liver and an equal percentage by the kidneys (47). A key factor to obtain an optimal enhancement is a preserved hepatobiliary function: in this setting the maximum enhancement of the liver could be obtained in 20 minutes after contrast media administration. ...
Postoperative bile leakage is a common complication of abdominal surgical procedures and a precise localization of is important to choose the best management. Many techniques are available to correctly identify bile leaks, including ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI), being the latter the best to clearly depict "active" bile leakages. This paper presents the state of the art algorithm in the detection of biliary leakages in order to plan a percutaneous biliary drainage focusing on widely available and safe contrast agent, the Gb-EOB-DPA. We consider its pharmacokinetic properties and impact in biliary imaging explain current debates to optimize image quality. We report common sites of leakage after surgery with special considerations in cirrhotic liver to show what interventional radiologists should look to easily detect bile leaks.
... Comparing with other hepatobiliary-specific agents, for example gadopentetate dimeglumine (Gd-DTPA), the advantages of Gd-EOB-DTPA mainly in: 1) Gd-EOB-DTPA has dual channels of excretion that can be excreted by the biliary tract and kidneys at the same time, and the ratio of two ways is about 50% [20]. That is to say, when there is an excretion disorder in one of the two ways, it can be compensated by another way; 2) To achieve the same degree of development, Gd-EOB-DTPA requires only one quarter of the amount of Gd-DTPA [21]; 3) Compared with Gd-DTPA, Gd-EOB-DTP can reach developmental requirements 20 min after injection instead of 40 min, thus significantly reducing inspection time; (4) Gd-EOB-DTPA is safer because it causes less adverse reactions [22] (Table 2). ...
... От точности идентификации рака печени зависит эффективность хирургического вмешательства или нехирургического лечения, направленного на деструкцию опухоли. Важность выявления метастазов печени обусловлена тем, что полное удаление всех метастазов в печень позволяет улучшить прогноз излечения, особенно в случае колоректального рака [6]. Необходимо проводить дифференциальную диагностику и в группе доброкачественных ООП, так как гемангиомы и фокально-нодулярная гиперплазия (ФНГ) могут наблюдаться консервативно, тогда как в случае гепато целлюлярных аденом может потребоваться оперативное лечение, связанное с потенциальным риском их малигнизации и кровотечения [7]. ...
Purpose: to evaluate the diagnostic value of contrastenhanced ultrasound (CEUS) with SonoVue in differential diagnosis of focal liver lesions (FLL) in a multidisciplinary clinic in Russian Federation. Materials and methods . Bolus intravenous administration of 1.2 ml of SonoVue (Bracco Swiss CA, Switzerland) followed with 5ml saline flush was used for liver CEUS. We utilized the scanners Mindray DC-8 (Mindrаy, China), Logiq S8 (GE, USA), Philips Epiq 7 (Philips, Holland), SonoScape S9 (SonoScape, China), Hitachi Ascendus (Hitachi, Japan) with 3.0–5.0 MHz convex probes in specialized “contrast” mode with low mechanic index (MI 0.08–0.1). The study conferred 73 patients in the age between 18 and 84 years (mean age 49 years) with FLL. CEUS was performed in 22 patients with previously verified diagnosis, while the rest of patients underwent CEUS before the final diagnosis. Contrast-enhanced liver CT was performed in all patients. In 49 (67.12%) of 73 cases, a pathology was performed after a targeted core-needle biopsy or autopsy. Qualitative features of US contrast enhancement of FLL were evaluated. Results . Qualitative aspects of CEUS for differentiation of FLL were defined. The principal sign for diagnosis between benign and malignant masses with CEUS was hypoenhancement of malignant lesions in comparison to surrounding normal parenchyma in portal and late venous phase (p ≤ 0.01). Alternatively, hyper- or isoenhancement throughout late venous phase was characteristic for benign FLL. Diffuse heterogeneous contrast enhancement was indicative of malignant FLL, and homogeneous – for benign. Additional diagnostic feature (p ≤ 0.05) was the type of contrast enhancement in the arterial phase. Heterogeneous diffuse contrast enhancement was observed in malignant FLL, while homogeneous – in benign FLL. Peripheral nodular contrast enhancement with centripetal filling was characteristic for liver hemangioma, centrifugal filling with “spoke-wheel” vascular pattern – for FNH, and peripheral rim-like hyperenhancement with rapid achievement of hypoenhancement at the beginning of the portal phase – for liver metastasis. Conclusion. Complex analysis of qualitative characteristics of CEUS with SonoVue is a promising option for differential diagnosis of FLL (sensitivity 92.85%, specificity 91.3%, diagnostic accuracy 92.15%) and can be utilized in daily practice.
... Compared with gadopentetate dimeglumine, gadoxetic acid has a unique ethoxybenzyl (EOB) group, and normal hepatocyte specifically take up gadoxetic acid (with an approximately 50% uptake rate). Therefore, this contrast agent may provide useful information to distinguish abnormal hepatocytes (including HCC) from normal ones [21,22]. Golfier R et al. have shown that gadoxetic acid has the capability to identify HCC precursors and determine their biological behaviour [23]. ...
Abstract Purpose The goal of this study was to investigate the Liver Imaging Reporting and Data System (LI-RADS) v.2017 for the categorization of hepatocellular carcinomas (HCCs) with gadoxetic acid compared with gadopentetate dimeglumine-enhanced 1.5-T magnetic resonance imaging (MRI). Material and methods We included 141 high-risk patients with 145 pathologically-confirmed HCCs who first underwent gadopentetate dimeglumine-enhanced 1.5-T followed by gadoxetic acid-enhanced 1.5-T MRI. Two independent radiologists evaluated the presence or absence of major HCC features and assigned LI-RADS categories after considering ancillary features on both MRIs. Finally, the sensitivity of LI-RADS category 5 (LR-5) and the frequencies of major HCC features were compared between gadoxetic acid- and gadopentetate dimeglumine-enhanced 1.5-T MRI using the Wilcoxon test. Results The sensitivity of LR-5 for diagnosing HCCs was significantly different between gadoxetic acid- and gadopentetate dimeglumine-enhanced MRI (73.8% [107/145] vs 26.2% [38/145], P
... Some studies have indicated that without reaching statistical significance, Gd-EOB-DTPA can influence DWI and T2-weighted images by causing higher magnetic susceptibility and T2 shortening [23,24]. In general, the DHBP with Gd-EOB-DTPA is acquired about 20 min after contrast administration, because at this time normal hepatocytes reach [25]. However, the time of contrast uptake may differ between individuals because the hepatic elimination pathway is related to hepatocyte function [26]. ...
Objectives:
To assess if the administration of gadoxetate disodium (Gd-EOB-DTPA) significantly affects hepatic magnetic resonance elastography (MRE) measurements in the delayed hepatobiliary phase (DHBP).
Methods:
A total of 47 patients (15 females, 32 males; age range 23-78 years, mean 54.28 years) were assigned to standard hepatic magnetic resonance imaging (MRI) with application of Gd-EOB-DTPA and hepatic MRE. MRE was performed before injection of Gd-EOB-DTPA and after 40-50 min in the DHBP. Liver stiffness values were obtained before and after contrast media application and differences between pre- and post-Gd-EOB-DTPA values were evaluated using a Bland-Altman plot and the Mann-Whitney-Wilcoxon test. In addition, the data were compared with regard to the resulting fibrosis classification.
Results:
Mean hepatic stiffness for pre-Gd-EOB-DTPA measurements was 4.01 kPa and post-Gd-EOB-DTPA measurements yielded 3.95 kPa. We found a highly significant individual correlation between pre- and post-Gd-EOB-DTPA stiffness values (Pearson correlation coefficient of r = 0.95 (p < 0.001) with no significant difference between the two measurements (p =0.49)). Bland-Altman plot did not show a systematic effect for the difference between pre- and post-stiffness measurements (mean difference: 0.06 kPa, SD 0.81). Regarding the classification of fibrosis stages, the overall agreement was 87.23% and the intraclass correlation coefficient was 96.4%, indicating excellent agreement.
Conclusions:
Administration of Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver in the DHBP. Therefore, MRE can be performed in the DHBP.
Key points:
• MRE of the liver can reliably be performed in the delayed hepatobiliary phase. • Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver. • MRE performed in the delayed hepatobiliary-phase is reasonable in patients with reduced liver function.
... Hepatobiliary contrast agents such as gadoxetic acid and/or gadobenate dimeglumine improve the detection and characterization of focal liver lesions by representing the vascularity and the presence/absence of hepatocellular contrast uptake at one time [45,46] . When liver metastases are the cause for ALPPS, preoperative MRI with diffusion-weighted imaging and hepatobiliary contrast agents should be regarded as the method of choice for detailed identification of small lesions potentially affecting ALPPS feasibility or FLR cleaning up [47] . ...
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a recently introduced technique aimed to perform two-stage hepatectomy in patients with a variety of primary or secondary neoplastic lesions. ALPSS is based on a preliminary liver resection associated with ligation of the portal branch directed to the diseased hemiliver (DH), followed by hepatectomy after an interval of time in which the future liver remnant (FLR) hypertrophied adequately (partly because of preserved arterialization of the DH). Multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) play a pivotal role in patients’ selection and FLR assessment before and after the procedure, as well as in monitoring early and late complications, as we aim to review in this paper. Moreover, we illustrate main abdominal MDCT and MRI findings related to ALPPS.
... The dose for its administration is 0.1 mmol/kg. Gadoxetic acid has different pharmacokinetic properties: it is generally excreted in a percentage of 50% and 50%, respectively, by the liver and by the kidneys; in the liver, mechanisms of excretion involve multidrug resistance-associated proteins (MRPs) [30]. When hepatobiliary function is preserved, maximum enhancement in the hepatic parenchyma is reached 20 minutes after its administration, whereas gadobenate dimeglumine needs at least 60 minutes. ...
Since its introduction, MRCP has been improved over the years due to the introduction of several technical advances and innovations. It consists of a noninvasive method for biliary tree representation, based on heavily T2-weighted images. Conventionally, its protocol includes two-dimensional single-shot fast spin-echo images, acquired with thin sections or with multiple thick slabs. In recent years, three-dimensional T2-weighted fast-recovery fast spin-echo images have been added to the conventional protocol, increasing the possibility of biliary anatomy demonstration and leading to a significant benefit over conventional 2D imaging. A significant innovation has been reached with the introduction of hepatobiliary contrasts, represented by gadoxetic acid and gadobenate dimeglumine: they are excreted into the bile canaliculi, allowing the opacification of the biliary tree. Recently, 3D interpolated T1-weighted spoiled gradient echo images have been proposed for the evaluation of the biliary tree, obtaining images after hepatobiliary contrast agent administration. Thus, the acquisition of these excretory phases improves the diagnostic capability of conventional MRCP—based on T2 acquisitions. In this paper, technical features of contrast-enhanced magnetic resonance cholangiography are briefly discussed; main diagnostic tips of hepatobiliary phase are showed, emphasizing the benefit of enhanced cholangiography in comparison with conventional MRCP.
... Patients who had undergone MRI had typical findings including slightly hyperintense on T2-weighted images, slightly hypointense on T1-weighted images, a hyperintense central scar on T2-weighted images and arterial enhancement without delayed washout. Current studies consistently show that MRI using hepatobiliary-specificity contrast agents such as gadoxetic acid (Gd-EOB-DTPA) allows for higher diagnostic accuracy of FNH, due to the mechanism that uptake of Gd-EOB-DTPA is only achieved by functional hepatocytes and FNH is considered as a nonneoplastic lesion [8]. In general, typical imaging features could help radiologists to diagnose FNH more confidently. ...
Background: New-onset hepatic nodules mostly are hepatocellular carcinomas in patients with viral hepatitis. Focal Nodular Hyperplasia (FNH) is the second most common benign liver tumor, which usually does not recur after surgical resection. We present a case of hepatitis B virus infected female with a new-onset FNH during pregnancy, which has not been reported before, to not only put an emphasis on the diagnostic accuracy of FNH but also avoid unnecessary surgical intervention. Case presentation: The 28-year-old Chinese female with chronic hepatitis B virus infection who underwent a resection of FNH in the left lobe of the liver three years ago, was found to present with a new-onset solid lesion in the right lobe of the liver. Contrast-Enhanced Ultrasound (CEUS) demonstrated a typical FNH of spoke wheel pattern enhancement in the arterial phase, still enhanced during the portal venous and delayed phases with a central stellate scar, which showed a similar enhancement pattern on contrast-enhanced CT and MRI. Finally, a core needle biopsy of the suspected lesion was confirmed to be FNH. Conclusion: Regenerate of FNH may also occur in patients with chronic hepatitis B, which was known as a risk factor for the occurrence of hepatocellular carcinoma. Diagnosis of FNH can be made definitely and non-invasively through the appliance of modern imaging modalities with typical performance of imaging features.
... R. et al had shown that EOB-MRI has the capability of identifying the HCC precursors and portraying their biological behaviors, thus rapidly becoming a key imaging tool for the diagnosis of HCC and its precursors [5]. Furthermore, one study demonstrated that magnetic resonance imaging (MRI) using gadoxetic acid provided more accurate diagnosis in discriminating focal nodular hyperplasia (FNH) from hepatic adenoma (HA), identification of early HCC and pre-operative assessment of metastasis in liver parenchyma [6]. Diffusion-weighted imaging (DWI) can provide cellular information of HCC and also has been widely applied in lesion detection, lesion characterization, and assessment of treatment response to chemotherapeutic agents. ...
Objective:
Gadoxetic acid disodium (Gd-EOB-DTPA) is a magnetic resonance imaging (MRI) contrast agent to target the liver cells with normal function. In clinical practice, the Gd-EOB-DTPA produces high quality hepatocyte specific image 20 minutes after intravenous injection, so DWI sequence is often performed after the conventional dynamic scanning. However, there are still some disputes about whether DWI sequence will provide more effective diagnostic information in clinical practice. This study aimed to explore the diagnostic value of combining Gd-EOB-DTPA-enhanced MRI and DWI in the detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease.
Methods:
A systematic literature search was performed in the PubMed and Cochrane library database up to March 2015. The quality assessment of diagnostic accuracy studies (QUADAS) was used to evaluate the quality of studies. Heterogeneous test on the included literature was performed by using the software Review Manager 5.3. The MetaDiSc 1.4 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio; meanwhile the summary receiver operating characteristics (SROC) curve was drawn to compare the diagnostic performance.
Results:
A total of 13 literatures were included in this study. In 8 literatures regarding HCC diagnosis based on Gd-EOB-DTPA-enhanced MRI, the pooled sensitivity: 0.90 (95% confidence interval (CI): 0.88-0.93); specificity: 0.89 (95% CI: 0.85-0.92); positive likelihood ratio: 8.60 (95% CI: 6.20-11.92); negative likelihood ratio: 0.10 (95% CI: 0.08-0.14) were obtained. The area under curve (AUC) and Q values were 0.96 and 0.90, respectively. In 5 literatures relating to HCC diagnosis by combination of Gd-EOB-DTPA-enhanced MRI and DWI sequence, the pooled sensitivity: 0.88 (95% CI: 0.85-0.91), specificity: 0.96 (0.94-0.97), positive likelihood ratio: 19.63 (12.77-30.16), negative likelihood ratio: 0.10 (0.07-0.14) were obtained. The AUC value was 0.9833 and Q value was 0.9436. The AUC value of comprehensive evaluation method was significantly higher than that of Gd-EOB-DTPA-enhanced MRI alone(P<0.05).
Conclusion:
Combination of Gd-EOB-DTPA-enhanced MRI and DWI sequence significantly improves in both the diagnostic accuracy and specificity of chronic liver disease-associated HCC.
... Среди злокачественных новообразований в печени чаще встречаются метастазы (гипер-и гиповаскулярные). При циррозе печени наиболее важное значение имеет ранняя диагностика гепатоцеллюлярного рака (ГЦР) [23]. В предоперационном периоде хирургу важно знать: 1) является данное очаговое образование печени доброкачественным или злокачественным; 2) число и локализацию очагов в печени по отношению к сосудам и прилежащим органам; 3) наличие внепеченочного распространения злокачественной опухоли [20]. ...
... The median (range) size of DLM before chemotherapy was 10 (4-10) mm for tumours that were identified during surgery and 8 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) mm for those that were undetected during surgery, without difference between groups (P = 0.424). ...
Chemotherapy is often used before a resection for colorectal liver metastases. After chemotherapy, metastases may disappear on cross-sectional imaging but residual metastatic disease may still exist. The aim of this retrospective study was to investigate the impact of new advancements in imaging technology such as magnetic resonance imaging (MRI) with liver-specific contrast (Gd-EOB-DTPA) and contrast-enhanced intra-operative ultrasound (CE-IOUS) on disappearing liver metastases (DLM).
Twenty-nine patients with one or more DLM undergoing surgical exploration were included. Pre-operative imaging consisted of contrast-enhanced multi-detector computed tomography (MDCT) and/or MRI with liver-specific contrast. At surgery, CE-IOUS was used when tumours known from pre-chemotherapy imaging were not found by inspection or intra-operative ultrasound.
Patients presented 66 DLM. At surgical exploration, 42 DLM were identified and treated (64%). CE-IOUS detected one additional DLM not found by intra-operative ultrasound. For metastases ≤10 mm on histological analysis, imaging sensitivities for MRI and MDCT before surgery but after chemotherapy were 26/49 (53%) and 24/66 (36%), respectively.
A majority of DLM are identified during surgery using intra-operative ultrasound, with only little additional value of CE-IOUS. The sensitivities of post-chemotherapy imaging modalities for small metastases are low in the setting of DLM. For surgical planning, an optimized pre-chemotherapy imaging is essential.
© 2015 International Hepato-Pancreato-Biliary Association.
... It is accepted that all hepatic adenomas should be considered for resection due to the malignant potential and risk of rupture, although surgery is not commonly undertaken for lesions <5 cm in diameter [3]. The use of multiphase MRI with gadoxetic acid contrast has the benefit of an additional phase specific to hepatocytes, as it is processed in the same manner as bile salts [7]. ...
Hepatic solitary fibrous tumor (HSFT) is a very rare benign liver tumor without well-defined findings on imaging. Even with multiphase advanced contrast-enhanced liver imaging, a definitive preoperative diagnosis is impossible. The diagnostic process can be further complicated when there are two concurrent lesions with different radiologic appearances. Here, we compare the findings of a commonly encountered liver lesion, hepatic hemangioma, with those of an exceedingly rare lesion, HSFT.
Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2015.
... These gadolinium-based contrast agents help differentiate FNH from HCA and other adenomas as bile ductuli are present in FNH as opposed to adenoma, allowing for FNH to appear iso/hyperintense as compared to the hypointense appearance of HCA and adenoma. 47 In fact, recent data has shown that diagnostic accuracy and sensitivity has significantly improved for the detection of focal solid hepatic lesions through the use of these gadolinium-based contrast agents. 48 Pathology On gross pathology, FNH is generally a solitary (80 % of the cases), 35 coarsely nodular, brown or yellowish-gray lesion of variable size (usually less than 5 cm but can reach up to 20 cm). ...
Recently, there has been a growing interest in solid benign liver tumors as the understanding of the pathogenesis and molecular underpinning of these lesions continues to evolve. We herein provide an evidence-based review of benign solid liver tumors with particular emphasis on the diagnosis and management of such tumors.
A search of all available literature on benign hepatic tumors through a search of the MEDLINE/PubMed electronic database was conducted.
New diagnostic and management protocols for benign liver tumors have emerged, as well as new insights into the molecular pathogenesis. In turn, these data have spawned a number of new studies seeking to correlate molecular, clinicopathological, and clinical outcomes for benign liver tumors. In addition, significant advances in surgical techniques and perioperative care have reduced the morbidity and mortality of liver surgery. Despite current data that supports conservative management for many patients with benign liver tumors, patients with severe preoperative symptomatic disease seem to benefit substantially from surgical treatment based on quality of life data.
Future studies should seek to further advance our understanding of the underlying pathogenesis and natural history of benign liver tumors in order to provide clinicians with evidence-based guidelines to optimize treatment of patients with these lesions.
Aim. Determining the role of ultrasound examination in the diagnostics of liver metastases at the preoperative stage. Methods. 518 patients with secondary tumors in the liver underwent ultrasonic study (US). The results were compared with the data of other methods, biopsy, surgical palpation and histopathalogical study of the resected samples. Results. US strategy of metastasis diagnostics evaluates the number, size, and localization of lesions; the data remain valid for about a month. These data are used in surgery planning considering individual course of diseases and chemotherapy results. US metastasis diagnostics sensitivity, specificity and accuracy were 95.2%, 26.8%, 89.8%, respectively. We developed a methodology for accurate determination of lesion sites in the liver. The study showed that chemotherapy could worsen US results. The authors give practical recommendations for optimization ofpreoperative diagnostics. Conclusion. Ultrasound diagnostics demonstrated high effectiveness in determination of number, size, and precise localization of metastatic liver lesions that allows recommending this method for wide use in surgery planning.
To determine the performance of diagnostic algorithm of adding hepatobiliary phase (HBP) images in Gd-EOB-DTPA-enhanced MRI for the detection of hepatocellular carcinoma (HCC) measuring up to 3 cm in patients with chronic liver disease.
We searched multiple databases from inception to April 10, 2020, to identify studies on using Gd-EOB-DTPA-enhanced MRI for the diagnostic accuracy of HCC (≤ 3 cm) in patients with chronic liver disease. The diagnostic algorithm of Gd-EOB-DTPA-enhanced MRI with HBP for HCC was defined as a nodule showing hyperintensity during arterial phase and hypointensity during the portal venous, delayed, or hepatobiliary phases. For gadoxetic acid–enhanced MRI without HBP, the diagnostic criteria were a nodule showing arterial enhancement and hypointensity on the portal venous or delayed phases. The data were extracted to calculate summary estimates of sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and summary receiver operating characteristic (sROC) by using a bivariate random-effects model.
Twenty-nine studies with 2696 HCC lesions were included. Overall Gd-EOB-DTPA-enhanced MRI with HBP had a sensitivity of 87%, specificity of 92%, and the area under the sROC curve of 95%. The summary sensitivity of Gd-EOB-DTPA-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01).
Gd-EOB-DTPA-enhanced MRI with HBP showed higher sensitivity than that without HBP and had comparable specificity for diagnosis of HCC in patients with chronic liver disease.
• Hypointensity on HBP is a major feature for diagnosis of HCC.
• Extending washout appearance to the transitional or hepatobiliary phase on Gd-EOB-DTPA provides favorable sensitivity and comparable specificity for diagnosis HCC.
• The summary sensitivity of gadoxetic acid–enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01) for diagnosis of HCC in patients with chronic liver disease.
Purpose
Evaluating the performance of free-breathing dynamic T1-weighted imaging (T1WI) using compressed sensing golden-angle radial sparse parallel imaging (CS-GRASP) in non-cooperative patients compared with a general group.
Method
This retrospective study included patients who underwent gadoxetic acid-enhanced liver MRI using CS-GRASP at 3T between March 2018 and October 2019. Patients were divided chronologically, into one of two groups: Group 1, who underwent MRI during the sequence implementation period regardless of breath-hold capability; and Group 2, who underwent MRI from June 2018 due to limited breath-hold capability. Three radiologists evaluated motion and streak artifacts as well as overall image quality on a four-point scale at the precontrast phase, late arterial phase (LAP) and portal venous phase (PVP). Intra-individual comparisons were made between sequences in each group.
Results
We identified 102 patients, who were divided into either Group 1 (n = 41) or 2 (n = 61). For the LAP, the former group had higher image quality (3.22 ± 0.65 vs. 2.95 ± 0.61, P < 0.001) and less streak artifact (2.96 ± 0.56 vs. 2.74 ± 0.57, P = 0.001) than the latter. However, there was no significant difference between the two groups regarding either the proportion of patients with acceptable motion artifact, at 92.7% (38/41) for Group 1 vs. 96.7% (59/61) for Group 2, or that of patients with acceptable image quality at 80.5% (33/41) for Group 1 vs. 65.6% (40/61) for Group 2 (P > 0.05). In intra-individual comparisons, portal phase showed the highest image quality than the others in both groups (P < 0.001).
Conclusions
Acceptable image quality for the LAP in non-cooperative patients was provided with a success rate of over 50% via free-breathing T1WI using CS-GRASP.
Nowadays, it is difficult to overestimate the role of cross-sectional imaging in the diagnosis of focal and diffuse liver diseases. In magnetic resonance imaging (MRI) there is a unique opportunity to use hepatospecific contrast agents compared with other visualization techniques. Gadoxetic acid is a hepatospecific magnetic resonance contrast agent which has the extracellular contrast agent properties and hepatotropic property. About half of the administered dose of gadoxetic acid enters into functioning hepatocytes through cell membrane transporters and then is excreted into the bile ducts and sinusoidal space. The obtained hepatobiliary phase provides information about the structural features of the focal liver lesions, improving their detection and differential diagnosis. In addition it allows to assess the anatomical and functional conditions of the hepatobiliary system. This article describes clinical applications of MRI with gadoxetic acid and its benefits, visualization principles of different focal liver lesions in hepatobiliary phase and features of the obtained images.
Hepatocellular carcinoma in patients with hepatitis C in the absence of cirrhosis is uncommon. We demonstrate the importance of morphofunctional magnetic resonance imaging (MRI) with a hepatospecific contrast agent by describing an asymptomatic female patient with HCV, who presented with a nodule detected on ultrasound. She underwent inconclusive computed tomography, presenting no signs of chronic liver disease. MRI with hepatospecific contrast providing functional information combined with the superior tissue contrast inherent to this method stands out for its greater accuracy with the possibility of not resorting to invasive diagnostic methods. With increasing experience and the dissemination of this new diagnostic modality in the medical field, its use and other potential benefits of morphofunctional MRI with hepatospecific contrast agents may be established, benefiting patients with challenging focal liver lesions.
Objectives
To review the gadoxetic acid disodium (EOB)-enhanced magnetic resonance (MR) imaging features of cholangiolocellular carcinoma (CoCC) of the liver and compare them with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). MethodsEOB-enhanced MR images of 19 patients with CoCC, 23 with ICC, and 51 with HCC were retrospectively evaluated qualitatively and quantitatively. Univariate and multivariate analyses were performed to determine the characteristic MR features of CoCC with histopathological–imaging correlation. ResultsMultivariate logistic regression analysis showed that dot-/band-shaped internal enhancement during the arterial and portal phases (P < 0.001), and larger arterial ring enhancement ratio (CoCC, 0.13 ± 0.04; ICC, 0.074 ± 0.04; P = 0.013) were significantly independently associated with CoCC in contrast to ICC, whereas several MR features including progressive enhancement during the portal and late phases (P < 0.001), target appearance in the hepatocyte phase (P = 0.004), and vessel penetration (P = 0.013) were significantly more frequently associated with CoCC than HCC. The dot-/band-like internal enhancement (78.9% of CoCCs) histopathologically corresponded to the tumour cell nest with vascular proliferations and retained Glisson's sheath structure. ConclusionsEOB-enhanced MR features of CoCC largely differ from those of HCC but are similar to those of ICC. However, the finding of thicker arterial ring enhancement with dot-/band-like internal enhancement could help differentiate CoCC from ICC. Key Points• Gadoxetic acid-enhanced MR features of cholangiolocellular carcinoma (CoCC) resembled those of intrahepatic cholangiocarcinoma (ICC).• Gadoxetic acid-enhanced MR features of CoCC largely differed from those of hepatocellular carcinoma.• Dot-/band-like internal enhancement of CoCC may be helpful for differentiating from ICC.• Arterial ring enhancement of CoCC was larger than that of ICC.
The current classification system of liver segmental anatomy describes the liver as divided into eight independent functioning units or segments, each of which is served by its own vascular pedicle and biliary drainage. The current standard MRI examination of the liver includes a T2-weighted sequence, a T1-weighted sequence, and a dynamic contrast-enhanced sequence. The need for more accurate detection and characterization of the full spectrum of liver pathology has been the major impetus for continued development in intravenous contrast agents. Biliary hamartomas are benign biliary malformations, which are currently considered as part of the spectrum of fibropolycystic diseases of the liver due to ductal plate malformation. Characterization of focal liver lesions as benign or malignant is important because patients with known primary malignancies commonly have small hepatic lesions that are benign cysts or hemangiomas. Patients with congestive heart failure may present with hepatomegaly and hepatic enzyme elevations.
Aim:
To validate the usefulness of diffusion-weighted imaging (DWI) in the differentiation of high-flow haemangiomas showing pseudo-washout appearance on gadoxetic acid-enhanced hepatic MRI from small hypervascular hepatocellular carcinomas (HCCs).
Materials and methods:
DWI (b=50, 800 s/mm(2)) with apparent diffusion coefficient (ADC) maps for 50 haemangiomas (6.4±2.9 mm) showing intense enhancement on arterial dominant phase imaging and hypointensity on transitional and/or hepatobiliary phase imaging during gadoxetic acid-enhanced MRI were retrospectively analysed and compared with that of 113 hypervascular HCCs (12.8±3.7 mm). In addition to measurement of mean ADC values on DWI and contrast-to-noise ratio (CNR) on corresponding T2-weighted imaging, qualitative analysis of DWI was performed for each lesion by two independent observers using a five-point scale.
Results:
Both of mean ADC value (1.902 versus 0.997×10(-3) mm(2)/s) and mean CNR (119.2 versus 36.9) for haemangioma were significantly larger than for HCC (p<0.001). On receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.995 for ADC values was significantly larger than 0.915 for CNRs (p=0.002). When the ADC value of 1.327×10(-3) mm(2)/s was used as the threshold for the diagnosis of haemangioma, the sensitivity and specificity were 98% and 97.3%, respectively. The mean sensitivity and specificity of qualitative analysis for the differentiation of haemangioma from HCC were 92% and 99.1%, respectively.
Conclusion:
For high-flow small haemangiomas showing pseudo-washout appearance during gadoxetic acid-enhanced hepatic MRI, high b-factor DWI including an ADC map may provide additional information to enhance the confidence to exclude small hypervascular HCCs.
To determine MR-imaging features for the differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver.
107 consecutive patients without liver cirrhosis (46 male; 45±14 years) who underwent liver resection due to suspicion of HCC were included in this multi-center study. The following imaging features were assessed: lesion diameter and demarcation, satellite-lesions, central-scar, capsule, fat-content, hemorrhage, vein-infiltration and signal-intensity (SI) on native T1-, T2- and dynamic-enhanced T1-weighted images (center versus periphery). In addition, contrast-media (CM) uptake in the liver specific phase was analyzed in a sub-group of 42 patients.
Significant differences between HCC (n=55) and benign lesions (n=52) were shown for native T1-, T2- and dynamic-enhanced T1-SI, fat-content, and satellite-lesions (all, P<.05). Independent predictors for HCC were T1-hypointensity (odds-ratio, 4.81), T2-hypo-/hyperintensity (5.07), lack of central tumor-enhancement (3.36), and satellite-lesions (5.78; all P<0.05). Sensitivity and specificity of HCC was 91% and 75% respectively for two out-of four independent predictors, whereas specificity reached 98% for all four predictors. Sub-analysis, showed significant differences in liver specific CM uptake between HCC (n=18) and benign lesions (n=24; P<0.001) and revealed lack of liver specific CM uptake (odds-ratio, 2.7) as additional independent feature for diagnosis of HCC.
Independent MRI features indicating HCC are T1-hypointensity, T2-hypo- or hyperintensity, lack of central tumor-enhancement, presence of satellite-lesions and lack of liver specific CM-uptake. These features may have the potential to improve the diagnosis of HCC in the non-cirrhotic liver.
Copyright © 2015. Published by Elsevier Ireland Ltd.
IntroductionHepatocellular adenoma (HCA) is a rare benign tumour mainly found in women who have been receiving oral contraceptives [1].According to recent studies, HCAs are currently categorized in four distinct genetic and pathologic subtypes as follows: inflammatory HCA, hepatocyte-nuclear-factor-1-alpha-(HNF-1α-mutated) HCA, β-catenin-mutated HCA and “unclassified” subtype [2, 3].Inflammatory HCA is also known as telangiectatic HCA and previously referred to as telangiectatic focal nodular hyperplasia (FNH) [4, 5]. This particular subtype of HCA has specifically been linked to an increased body mass index and a generalized systemic inflammatory condition [4, 6].Magnetic resonance imaging (MRI) is now established as the method of choice to evaluate focal liver lesions [7, 8]; furthermore, thanks to the introduction of hepatobiliary contrast agents, the possibility to characterize lesions is really improved [9, 10].Gadobenate dimeglumine and gadoxetic acid disodium (Gd-EOB-DTPA) are h ...
To determine which dynamic phase(s) of gadoxetic acid-enhanced MRI is most appropriate to assess "washout" in the noninvasive diagnosis of hepatocellular carcinoma (HCC) based on hemodynamic pattern.
In this retrospective cohort study, 288 consecutive patients with chronic liver disease presented with 387 arterially enhancing nodules (292 HCCs, 95 non-HCCs) (≥1 cm) on gadoxetic acid-enhanced MRI. All HCCs were confirmed by histopathology or by their typical enhancement pattern on dynamic liver CT. MR imaging diagnosis of HCC was made using criteria of arterial enhancement and hypointensity relative to the surrounding parenchyma (1) on the portal-venous phase (PVP), (2) on the PVP and/or transitional phase (TP), or (3) on the PVP and/or TP, and/or hepatobiliary phase (HBP).
For the noninvasive diagnosis of HCC, criterion 1 provided significantly higher specificity (97.9 %; 95 % confidence interval, 92.6 - 99.7 %) than criteria 2 (86.3 %; 77.7 - 92.5 %), or 3 (48.4 %; 38.0 - 58.9 %). Conversely, higher sensitivity was obtained with criterion 3 (93.8 %; 90.4 - 96.3 %) than with criterion 2 (86.6 %; 82.2 - 90.3 %) or 1 (70.9 %; 65.3 - 76.0 %).
To make a sufficiently specific diagnosis of HCC using gadoxetic acid-enhanced MRI based on typical enhancement features, washout should be determined on the PVP alone rather than combined with hypointensity on the TP or HBP.
• Gadoxetic acid-enhanced MRI enhancement features can be used to diagnose HCC. • Washout should be determined on the PVP alone for high specificity. • Hypointensity on the TP or HBP increases sensitivity but lowers specificity.
Hepatocyte specific contrast agents including gadoxetic acid and gadobenate dimeglumine are very useful to diagnose various benign and malignant focal hepatic lesions and even helpful to estimate hepatic functional reservoir. The far delayed phase image referred to as the hepatobiliary phase makes the sensitivity of detection for malignant focal hepatic lesions increased, but specificity of malignant diseases, including hepatocellular carcinoma, metastasis and cholangiocarcinoma, characterization remained to be undetermined.
To compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging with that of triple-phase multidetector-row computed tomography (MDCT) in the detection of liver metastasis.
Our institutional review board approved this retrospective study and waived informed consent. The study population consisted of 51 patients with hepatic metastases and 62 patients with benign hepatic lesions, who underwent triple-phase MDCT and gadoxetic acid-enhanced MRI within one month. Two radiologists independently and randomly reviewed MDCT and MRI images regarding the presence and probability of liver metastasis. In order to determine additional value of hepatobiliary-phase (HBP), the dynamic-MRI set alone and combined dynamic-and-HBP set were evaluated, respectively. The standard of reference was a combination of pathology diagnosis and follow-up imaging. For each reader, diagnostic accuracy was compared using the jackknife alternative free-response receiver-operating-characteristic (JAFROC).
For both readers, average JAFROC figure-of-merit (FOM) was significantly higher on the MR image sets than on the MDCT images: average FOM was 0.582 on the MDCT, 0.788 on the dynamic-MRI set and 0.847 on the combined HBP set, respectively (p < 0.0001). The differences were more prominent for small (≤ 1 cm) lesions: average FOM values were 0.433 on MDCT, 0.711 on the dynamic-MRI set and 0.828 on the combined HBP set, respectively (p < 0.0001). Sensitivity increased significantly with the addition of HBP in gadoxetic acid-enhanced MR imaging (p < 0.0001).
Gadoxetic acid-enhanced MRI shows a better performance than triple-phase MDCT for the detection of hepatic metastasis, especially for small (≤ 1 cm) lesions.
To elucidate the variety of ways early-stage hepatocellular carcinoma (HCC) can appear on magnetic resonance (MR) imaging by analyzing T1-weighted, T2-weighted, and gadolinium-enhanced dynamic studies.
Seventy-three patients with well-differentiated HCC (wHCC) or dysplastic nodules were retrospectively identified from medical records, and new histological sections were prepared and reviewed. The tumor nodules were categorized into three groups: dysplastic nodule (DN), wHCC compatible with Edmondson-Steiner grade I HCC (w1-HCC), and wHCC compatible with Edmondson-Steiner grade II HCC (w2-HCC). The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.
Among the 73 patients, 14 were diagnosed as having DN, 40 were diagnosed as having w1-HCC, and 19 were diagnosed as having w2-HCC. Hyperintensity measurements on T2-weighted axial images (T2WI) were statistically significant between DNs and wHCC (P = 0.006) and between DN and w1-HCC (P = 0.02). The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC. Hyperintensity on both T1W out-phase imaging (P = 0.007) and arterial enhancement on dynamic study (P = 0.005) showed statistically significant differences between w1-HCC and w2-HCC. The other imaging features revealed no significant differences between w1-HCC and w2-HCC.
In the follow-up for a cirrhotic nodule, increased signal intensity on T2WI may be a sign of malignant transformation. Furthermore, a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.
Diffusion-weighted imaging (DWI) is one of the magnetic resonance imaging (MRI) sequences providing qualitative as well as quantitative information at a cellular level. It has been widely used for various applications in the central nervous system. Over the past decade, various extracranial applications of DWI have been increasingly explored, as it may detect changes even before signal alterations or morphological abnormalities become apparent on other pulse sequences. Initial results from abdominal MRI applications are promising, particularly in oncological settings and for the detection of abscesses. The purpose of this article is to describe the clinically relevant basic concepts of DWI, techniques to perform abdominal DWI, its analysis and applications in abdominal visceral MR imaging, in addition to a brief overview of whole body DWI MRI.
In gadoxetic acid-enhanced liver magnetic resonance imaging(MRI), it is known that the pseudoglandular type of hepatocellular carcinoma (HCC) may demonstrate high signal intensity on 20-minutes delayed imaging unlike the microtrabecular counterpart. Herein we report a case of HCC which consisted of mixed components of hypo- and hyper-intensity in the hepatobiliary phase of gadoxetic acid-enhanced MRI, focusing on its imaging findings and pathologic features.
Objectives:
To correlate MR findings with pathology in steatotic FNHs and to compare the MR findings with those of other fatty tumours developed on noncirrhotic liver in a consecutive series of resected lesions.
Methods:
Our population included resected FNH with intralesional steatosis (n = 25) and other resected fatty tumours selected as controls (hepatocellular adenomas and angiomyolipomas, n = 34). Lesions were classified into three groups: those with typical FNH without (group 1) or with (group 2) fat on MR and those with atypical lesions (group 3). In group 3, diagnostic criteria for other fatty tumours were applied.
Results:
There were 9 lesions in group 1 (15.3 %), 4 in group 2 (16.8 %) and 46 in group 3 (77.9 %). Group 3 contained 12 FNHs (26 %) and all the other fatty tumours. In group 3, the association of lesion homogeneity, signal intensity similar to or slightly different from adjacent liver on in-phase T1- and T2-weighted sequences, and strong arterial enhancement was observed in 7/12 (58 %) of steatotic FNHs and 3/34 (9 %) of other tumours.
Conclusion:
On MR, fat within a typical FNH should not reduce the diagnostic confidence. We recommend further investigations including liver biopsy if necessary when fatty tumours exhibit atypical MR findings.
Diffusion-weighted magnetic resonance imaging (DWI) is a well established method for the evaluation of intracranial diseases, such as acute stroke. DWI for extracranial application is more difficult due to physiological motion artifacts and the heterogeneous composition of the organs. However, thanks to the newer technical development of DWI, DWI has become increasingly used over the past few years in extracranial organs including the abdomen and pelvis. Most previous studies of DWI have been limited to the evaluation of diffuse parenchymal abnormalities and focal lesions in abdominal organs, whereas there are few studies about DWI for the evaluation of the biliopancreatic tract. Although further studies are needed to determine its performance in evaluating bile duct, gallbladder and pancreas diseases, DWI has potential in the assessment of the functional information on the biliopancreatic tract concerning the status of tissue cellularity, because increased cellularity is associated with impeded diffusion, as indicated by a reduction in the apparent diffusion coefficient. The detection of malignant lesions and their differentiation from benign tumor-like lesions in the biliopancreatic tract could be improved using DWI in conjunction with findings obtained with conventional magnetic resonance cholagiopancreatography. Additionally, DWI can be useful for the assessment of the biliopancreatic tract in patients with renal impairment because contrast-enhanced computed tomography or magnetic resonance scans should be avoided in these patients.
To evaluate the role of diffusion-weighted imaging (DWI) in the detection of focal liver lesions (FLLs), using a conventional magnetic resonance imaging (MRI) protocol.
Fifty-two patients (22 males, average age 55.6 years, range: 25-82 years), studied using a 1.5 Tesla magnetic resonance scanner, were retrospectively analyzed; detection of FLLs was evaluated by considering the number of lesions observed with the following sequences: (1) respiratory-triggered diffusion-weighted single-shot echo-planar (DW SS-EP) sequences; (2) fat-suppressed fast spin-echo (fs-FSE) T2 weighted sequences; (3) steady-state free precession (SSFP) images; and (4) dynamic triphasic gadolinium-enhanced images, acquired with three-dimensional fast spoiled gradient-echo (3D FSPGR). Two radiologists independently reviewed the images: they were blinded to their respective reports. DW SS-EP sequences were compared to fs-FSE, SSFP and dynamic gadolinium-enhanced acquisitions using a t-test. Pairs were compared for the detection of: (1) all FLLs; (2) benign FLLs; (3) malignant FLLs; (4) metastases; and (5) hepatocellular carcinoma (HCC).
Interobserver agreement was very good (weighted κ = 0.926, CI = 0.880-0.971); on the consensus reading, 277 FLLs were detected. In the comparison with fs-FSE, DW SS-EP sequences had a significantly higher score in the detection of all FLLs, benign FLLs, malignant FLLs and metastases; no statistical difference was observed in the detection of hepatocellular carcinoma (HCCs). In the comparison with SSFP sequences, DW SS-EP had significantly higher scores (P < 0.05) in the detection of all lesions, benign lesions, malignant lesions, metastases and HCC. All FLLs were better detected by dynamic 3D FSGR enhanced acquisition, with P = 0.0023 for reader 1 and P = 0.0086 for reader 2 in the comparison with DW SS-EP sequences; with reference to benign FLLs, DW SS-EP showed lower values than 3D FSPGR enhanced acquisition (P < 0.05). No statistical differences were observed in the detection of malignant lesions and metastases; considering HCCs, a very slight difference was reported by reader 1 (P = 0.049), whereas no difference was found by reader 2 (P = 0.06).
In lesion detection, DWI had higher scores than T2 sequences; considering malignant FLLs, no statistical difference was observed between DWI and dynamic gadolinium images.
To retrospectively evaluate the utility of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the differential diagnosis of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH).
This study had institutional review board approval; the requirement for informed consent was waived. Eighty-two patients (58 patients with FNH and 24 patients with HCAs) with 111 lesions were included in the study. There were 74 female patients and eight male patients (mean age, 41.9 years±13.2 [standard deviation]; age range, 11-78 years). Two readers reviewed all images in terms of signal intensity (SI) features on unenhanced, dynamic, and hepatobiliary phase images. For quantitative analysis, contrast enhancement ratio (CER), lesion-to-liver contrast (LLC), and SI ratio on dynamic and hepatobiliary phase images were calculated.
The CER of FNH in the arterial phase (mean, 94.3%±33.2) was significantly higher than that of HCAs (mean, 59.3%±28.1) (P<.0001). During the hepatobiliary phase, the LLC of FNH showed minimally positive values (mean, 0.05±0.01) and that of HCAs demonstrated strong negative values (mean, -0.67±0.24) (P<.0001). The area under the receiver operating characteristic curve of the hepatobiliary phase SI ratio for differentiation of the two tumors was 0.97, and a sensitivity of 92% and specificity of 91% were found with a cutoff value of 0.87. Among six FNH lesions that showed atypical hypointensity during the hepatobiliary phase, four had a large central scar, one contained a substantial fat component, and one had abundant radiating fibrous septa. Three HCAs were isointense during the hepatobiliary phase owing to severe hepatic steatosis.
Gadoxetic acid-enhanced MR imaging facilitates the differentiation of FNH from HCA.
This paper reports on issues relating to the optimal use of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA MR imaging) together with the generation of consensus statements from a working group meeting, which was held in Seoul, Korea (2010). Gd-EOB-DTPA has been shown to improve the detection and characterization of liver lesions, and the information provided by the hepatobiliary phase is proving particularly useful in differential diagnoses and in the characterization of small lesions (around 1-1.5 cm). Discussion also focused on advances in the role of organic anion-transporting polypeptide 8 (OATP8) transporters. Gd-EOB-DTPA is also emerging as a promising tool for functional analysis, enabling the calculation of post-surgical liver function in the remaining segments. Updates to current algorithms were also discussed.
A prospective study was performed on 14 patients with histologically proven focal nodular hyperplasia (FNH) using a hepatobiliary scan with trimethylbromoimino-diacetic acid (TBIDA) and a colloid scan with rhenium sulfur colloids. TBIDA uptake was relatively normal in the region of the tumor, but during the clearance phase 23/25 of the tumors were detected by a hot spot of radioactivity. Depending on the relative contrast achieved between the tumor and normal liver, this hot spot appeared early or later, but was always present at 60 min. In three tumors, a "doughnut" pattern was observed within the hot spot due to a central defect. Hypervascularization was observed during the perfusion phase in 76% of the tumoral sites and normal colloid uptake in only 64%. The detectability of FNH appears greater with TBIDA (92%) than with CT or MRI (84%). The high prevalence of hot spots may be due to careful technological conditions when obtaining hepatobiliary scans. Late images, overexposed films, multiple views and stimulation of gallbladder excretion increased tumor detectability. The hot spot sign may be a useful tool when combined with the results of other imaging modalities in the diagnosis of FNH. The peculiar pathology of FNH with fibrosis, hyperplastic hepatocytes and cholangiolar proliferation might explain this scintigraphic appearance.
The purpose of this study was to determine the usefulness of diffusion-weighted MR imaging with single-shot echoplanar imaging in characterizing focal hepatic lesions by apparent diffusion coefficient (ADC) and contrast-to-noise ratio (CNR) measurements.
Diffusion-weighted imaging on a 1.5-T MR unit was performed in 46 patients with 74 known focal hepatic lesions (11 hemangiomas, 15 metastases, and 48 hepatocellular carcinomas [HCCs]). Mean values for ADCs and CNRs of all lesions were calculated. Mean values for CNRs with diffusion-weighted imaging were also compared with those for breath-hold T2-weighted fast spin-echo images.
The mean values for ADCs were different for each type of tumor (5.39 x 10(-3) mm2/sec +/- 1.23 in hemangiomas, 2.85 x 10(-3) mm2/sec +/- 0.59 in metastases, and 3.84 x 10(-3) mm2/sec +/- 0.92 in HCCs), and each of them was significantly greater than the mean values for ADCs of the normal liver (2.28 x 10(-3) mm2/sec +/- 1.23 in normal liver [p < .05] except metastasis versus normal liver [p < .1]). Also, the mean values for ADCs were based on differences of ADC values. Only four (6%) of 63 malignant tumors (three HCCs and one metastasis) could not be differentiated from hemangiomas. The mean value for CNRs with diffusion-weighted images (14.4 +/- 8.54 in HCC and 29.0 +/- 6.79 in metastasis) was significantly higher than the mean values for CNRs obtained with T2-weighted fast spin-echo images in both metastases and HCCs (p < .05), whereas no significant difference was seen for hemangiomas.
Mean values for ADCs differed for the three types of the hepatic lesions and were higher than ADCs of the normal liver. We suggest that diffusion-weighted imaging may be useful for increased detection of HCCs and metastases and in distinguishing these entities from hemangiomas.
Optimal detection of focal hepatic lesions in patients with metastases can alter patient management and result in significant cost savings by reducing the number of unnecessary laparotomies for unresectable disease. Liver-specific MR imaging contrast agents (reticuloendothelial and hepatobiliary agents) offer greater lesion-to-liver contrast than the conventional extracellular fluid space MR imaging contrast agents (gadolinium chelates), which have a nonspecific distribution.
For the detection of hepatic metastases, although the work of Seneterre et al⁶¹ suggests that the accuracy of ferumoxide-enhanced MR imaging is equivalent to that of CTAP, other studies40, 67 find CTAP to be superior. Comparisons of reticuloendothelial agents and hepatobiliary agents for imaging liver metastases are lacking in the literature. Further studies comparing MR imaging enhanced with liver-specific contrast agents to CTAP are needed to determine if hepatic MR imaging can replace CTAP for the preoperative evaluation of hepatic metastases.
For the characterization of focal liver lesions, MnDPDP and ferumoxides have been added to the small list of FDA-approved contrast agents, and both can help to increase diagnostic specificity. Two of the hepatobiliary agents which are not yet approved, Gd-BOPTA and Gd-EOB-DTPA, have the potential of characterizing liver lesions during dynamic contrast enhancement (similar to Gd-DTPA) and during the hepatocyte phase (similar to MnDPDP), and may increase the detection of focal liver lesions.
PURPOSE/AIM
The purpose of this exhibit is: 1. To know image protocol of Gd-EOB-DTPA enhanced MRI 2. To review the various Gd-EOB-DTPA enhanced MRI appearances of the common benign and malignant hepatic tumors 3. To compare breath-hold three-dimensional (3D) Gd-EOB-DTPA enhanced MR cholangiography with HASTE MRCP in patient with various bile duct diseases
CONTENT ORGANIZATION
1. Contrast medium and application 2. Review of imaging findings of focal hepatic lesions benign lesions malignant lesions 3. Comparison of breath-hold three-dimensional (3D) Gd-EOB-DTPA enhanced MR cholangiography with HASTE MRCP benign disease malignant disease 4. Limitation and pitfalls 5. Future directions and summary
SUMMARY
The major teaching points of this exhibit are: 1. Gd-EOB-DTPA enhanced liver MR imaging is useful in detection and characterization of focal hepatic lesions 2. EOB-MR cholangiography is useful in the evaluation of biliary disease compare with HASTE MRCP 3. EOB-MR cholangiography has some pitfalls and limitations
The aim of our study was to evaluate the diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance (MR) imaging both in the detection of hepatocellular carcinoma (HCC) and precancerous lesions and in the assessment of their evolution.
A retrospective study was undertaken on 56 patients with chronic liver disease and suspected liver lesions. We evaluated the number, size and signal intensity of the nodules on dynamic and hepatobiliary MR images. Follow-up studies were carried out every 3 months. Statistical analysis was performed using the Fisher's exact test.
A total of 120 nodules were identified in 41 patients. Of these, 92/120 nodules (76.6 %; mean diameter 18.4 mm) showed the typical HCC vascular pattern: 90/92 nodules appeared hypointense and 2/92 were hyperintense on hepatobiliary phase images. An additional 28/120 hypointense, nonhypervascular nodules (23.3 %; mean diameter 11 mm) were detected on hepatobiliary phase images, 15 of which showed hypointensity also on the equilibrium phase images. During the 3- to 12-month follow-up, 14/28 nodules (mean diameter 13.3 mm) developed the typical vascular pattern of HCC.
Gadoxetic acid-enhanced MR imaging is useful for detecting HCC as well as hypovascular nodules with potential progression to HCC. Lesions measuring more than 10 mm in diameter are at higher risk of developing into HCC (p = 0.0128).
Based on recent clinical practice guidelines, imaging is largely replacing pathology as the preferred diagnostic method for determination of hepatocellular carcinoma (HCC). A variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography, are currently used to examine patients with chronic liver disease and suspected HCC. Advancements in imaging techniques such as perfusion imaging, diffusion imaging, and elastography along with the development of new contrast media will further improve the ability to detect and characterize HCC. Early diagnosis of HCC is essential for prompt treatment, which may in turn improve prognosis. Considering the process of hepatocarcinogenesis, it is important to evaluate sequential changes via imaging which would help to differentiate HCC from premalignant or benign lesions. Recent innovations including multiphasic examinations, high-resolution imaging, and the increased functional capabilities available with contrast-enhanced US, multidetector row CT, and MRI have raised the standards for HCC diagnosis. Although hemodynamic features of nodules in the cirrhotic liver remain the main diagnostic criterion, newly developed cellspecific contrast agents have shown great possibilities for improved HCC diagnosis and may overcome the diagnostic dilemma associated with small or borderline hepatocellular lesions. In the 20th century paradigm of medical imaging, radiological diagnosis was based on morphological characteristics, but in the 21st century, a paradigm shift to include biomedical, physiological, functional, and genetic imaging is needed. A multidisciplinary team approach is necessary to foster an integrated approach to HCC imaging. By developing and combining new imaging modalities, all phases of HCC patient care, including screening, diagnosis, treatment, and therapy, can be dramatically improved.
To compare the diagnostic efficacy of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) vs. multidetector computed tomography (MDCT) for the detection and classification of focal liver lesions, differentiated also for lesion entity and size; a separate analysis of pre- and postcontrast images as well as T2-weighted MRI sequences of focal and exclusively solid lesions was integrated.
Twenty-nine patients with 130 focal liver lesions underwent MDCT (64-detector-row; contrast medium iopromide; native, arterial, portalvenous, venous phase) and MRI (1.5-T; dynamic and tissue-specific phase 20min after application of Gd-EOB-DTPA). Hepatic lesions were verified against a standard of reference (SOR). CT and MR images were independently analysed by four blinded radiologists on an ordinal 6-point-scale, determining lesion classification and diagnostic confidence.
Among 130 lesions, 68 were classified as malignant and 62 as benign by SOR. The detection of malignant and benign lesions differed significantly between combined and postcontrast MRI vs. MDCT; overall detection rate was 91.5% for combined MRI and 80.4% for combined MDCT (p<0.05). Considering all four readers together, combined MDCT achieved sensitivity of 66.2%, specificity of 79.0%, and diagnostic accuracy of 72.3%; combined MRI reached superior diagnostic efficacy: sensitivity 86.8%, specificity 94.4%, accuracy 90.4% (p<0.05). Differentiated for lesion size, in particular lesions <20mm revealed diagnostic benefit by MRI. Postcontrast MRI also achieved higher overall sensitivity, specificity, and accuracy compared to postcontrast MDCT for focal and exclusively solid liver lesions (p<0.05).
Combined and postcontrast Gd-EOB-DTPA-enhanced MRI provided significantly higher overall detection rate and diagnostic accuracy, including low inter-observer variability, compared to MDCT in a single centre study.
Management of patients with a benign hepatocellular tumor relies largely on imaging data; the diagnosis of focal nodular hyperplasia (FNH) must be made with certainty using MRI, because no other clinical or laboratory data can help diagnosis. It is also essential to identify adenomas to manage them appropriately. The radiological report in these situations is therefore of major importance. However, there are diagnostic traps. The aim of this paper is to present the keys to the diagnosis of benign lesions and to warn of the main diagnostic pitfalls.
Purpose:
To evaluate the accuracy and confidence in diagnosing liver metastases using combined gadolinium-EOB-DTPA (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI)/diffusion-weighted imaging (DWI) in comparison to Gd-EOB-DTPA enhanced MRI and DWI alone.
Materials and methods:
Forty-three patients (age, 58 ± 13 years) with 89 liver lesions (28 benign, 61 malignant) underwent liver MRI for suspected liver metastases. Three image sets (DWI, Gd-EOB-DTPA and combined Gd-EOB-DTPA/DWI) in combination with unenhanced T1- and T2-weighted images were reviewed by three readers. Detection rates of focal liver lesions were assessed and diagnostic accuracy was evaluated by calculating the areas under the receiver-operating-characteristics curve (AUC). Confidence in diagnosis was evaluated on a 3-point scale. Histopathology and imaging follow-up served as the standard of reference.
Results:
Detection of liver lesions and confidence in final diagnosis for all readers were significantly higher for the combined Gd-EOB-DTPA/DWI dataset than for DWI. The combination of DWI and Gd-EOB-DTPA rendered a significantly higher confidence in final diagnosis (2.44 vs. 2.50) than Gd-EOB-DTPA alone for one reader. For two readers, accuracy in diagnosis of liver metastases was significantly higher for Gd-EOB-DTPA/DWI (AUCs of 0.84 and 0.83) than for DWI datasets (AUCs of 0.73 and 0.72). Adding DWI to Gd-EOB-DTPA did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA imaging alone.
Conclusion:
Addition of DWI sequences to Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA enhanced MRI alone in the diagnosis of liver metastases. However, the increase in diagnostic confidence might justify acquisition of DWI sequences in a dedicated MRI protocol.
Because virtually all patients with colonic cancer will undergo some form of surgical therapy, the role of preoperative imaging is directed at determining the presence or absence of synchronous carcinomas or adenomas and local or distant metastases. In contrast, preoperative staging for rectal carcinoma has significant therapeutic implications and will direct the use of radiation therapy, surgical excision, or chemotherapy. CT of the chest, abdomen, and pelvis is recommended for the initial evaluation for the preoperative assessment of patients with colorectal carcinoma. Although the overall accuracy of CT varies directly with the stage of colorectal carcinoma, CT can accurately assess the presence of metastatic disease. MRI using endorectal coils can accurately assess the depth of bowel wall penetration of rectal carcinomas. Phased-array coils provide additional information about lymph node involvement. Adding diffusion-weighted imaging to conventional MRI yields better diagnostic accuracy than conventional MRI alone. Transrectal ultrasound can distinguish layers within the rectal wall and provides accurate assessment of the depth of tumor penetration and perirectal spread, and PET and PET/CT have been shown to alter therapy in almost one-third of patients with advanced primary rectal cancer. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Objectives To compare the diagnostic accuracy and sensitivity of Gd-EOB-DTPA MRI and diffusion-weighted (DWI) imaging alone and in combination for detecting colorectal liver metastases in patients who had undergone preoperative chemotherapy. Methods Thirty-two consecutive patients with a total of 166 liver lesions were retrospectively enrolled. Of the lesions, 144 (86.8 %) were metastatic at pathology. Three image sets (1, Gd-EOB-DTPA; 2, DWI; 3, combined Gd-EOB-DTPA and DWI) were independently reviewed by two observers. Statistical analysis was performed on a per-lesion basis. Results Evaluation of image set 1 correctly identified 127/166 lesions (accuracy 76.5 %; 95 % CI 69.3–82.7) and 106/144 metastases (sensitivity 73.6 %, 95 % CI 65.6–80.6). Evaluation of image set 2 correctly identified 108/166 (accuracy 65.1 %, 95 % CI 57.3–72.3) and 87/144 metastases (sensitivity of 60.4 %, 95 % CI 51.9–68.5). Evaluation of image set 3 correctly identified 148/166 (accuracy 89.2 %, 95 % CI 83.4–93.4) and 131/144 metastases (sensitivity 91 %, 95 % CI 85.1–95.1). Differences were statistically significant (P Conclusions The combination of DWI with Gd-EOB-DTPA-enhanced MRI imaging significantly increases the diagnostic accuracy and sensitivity in patients with colorectal liver metastases treated with preoperative chemotherapy, and it is particularly effective in the detection of small lesions.
Key Points
• Accurate detection of colorectal liver metastases is essential to determine resectability. • Almost 80 % of patients are candidates for neoadjuvant chemotherapic treatment at diagnosis. After chemotherapy, metastases usually decrease, and drug-induced liver steatosis may be present. • The sensitivity of imaging is significantly inferior to that in chemotherapy-naïve patients. • DWI combined with Gd-EOB-DTPA increases sensitivity in detecting small metastases after chemotherapy.
Fifty-one focal nodular hyperplasia lesions from 36 patients were examined histologically. Serial sections and three-dimensional models were studied in selected cases. Lesions were multiple in 19% of patients. Thirty-four patients were female. One case had 11 focal nodular hyperplasia lesions and 7 hemangiomata in the liver. Three had astrocytoma and one had anomalous pulmonary venous drainage. Morphometric analysis revealed that the lesions were supplied by an anomalous artery larger than expected for the locale in the liver. This artery branched to form a spider-like structure and was usually not accompanied by a portal vein or duct. Each terminal arterial branch supplied a separate nodule 1 mm in diameter; adjacent nodules coalesced to form the focal nodular hyperplasia lesion. The arterial blood appeared to drain directly into the sinusoids of the nodule.
We propose that focal nodular hyperplasia is an hyperplastic response of the hepatic parenchyma to a preexisting arterial spider-like malformation. The frequent coexistence of focal nodular hyperplasia with other vascular and neuroendocrine anomalies suggest that the malformations are developmental in origin. The basic requirement for development of hepatic hyperplasia may be greater blood flow to a region compared to the adjacent parenchyma. This requirement appears to be met in the other forms of nodular transformation of the liver, i.e., nodular regenerative hyperplasia and partial nodular transformation.
To characterize imaging features of histologically proven hepatic adenoma (HA) as well as histologically and/or radiologically proven focal nodular hyperplasia (FNH) using delayed hepatobiliary MR imaging with 0.05 mmol/kg gadoxetic acid.
Five patients with six HAs with histological correlation were retrospectively identified on liver MRI studies performed with gadoxetic acid, and T1-weighted imaging acquired during the delayed hepatobiliary phase. Additionally, 23 patients with 34 radiologically diagnosed FNH lesions (interpreted without consideration of delayed imaging) were identified, two of which also had histological confirmation. Signal intensity ratios relative to adjacent liver were measured on selected imaging sequences.
All six hepatic adenomas (100%), which had histological confirmation, demonstrated hypointensity relative to adjacent liver on delayed imaging. Furthermore, all of the FNH (including 34 radiologically proven, 2 of which were also histologically proven) were either hyperintense (23/34, 68%) or isointense (11/34, 32%) relative to the adjacent liver on delayed imaging. None of the FNHs were hypointense relative to liver.
Distinct imaging characteristics of HA versus FNH on delayed gadoxetic acid-enhanced MRI, with adenomas being hypointense and FNH being iso- or hyperintense on delayed imaging may improve specificity for characterization, and aid in the differentiation of these two lesions.
The purpose of this study was to evaluate enhancement characteristics of hepatocellular adenomas (HCAs) using gadoxetic acid as a hepatocyte-specific MR contrast agent.
Twenty-four patients with histopathologically proven HCAs were retrospectively identified. MRI consisted of T1- and T2-weighted (w) sequences with and without fat saturation (fs), multiphase dynamic T1-w images, and fs T1-w images during the hepatobiliary phase. Standard of reference was surgical resection (n = 19) or biopsy (n = 5). Images were analysed for morphology and contrast behaviour including signal intensity (SI) measurement on T1-w images normalised to the pre-contrast base line.
In total 34 HCAs were evaluated. All HCAs showed enhancement in the arterial phase; 38 % of HCAs showed reduced contrast enhancement ("wash-out") in the venous phase. All HCAs showed enhancement (SI increase, 56 ± 53 %; P <0.001) in the hepatobiliary phase, although liver uptake was stronger (96 ± 58 %). Thus, 31 of all HCAs (91 %) appeared hypointense to the surrounding liver in the hepatobiliary phase, while 3 out of 34 lesions were iso-/hyperintense.
Gadoxetic acid accumulates in HCAs in the hepatobiliary phase, although significantly less than in surrounding liver. Thus, HCA appears in the vast majority of cases as a hypointense lesion on hepatobiliary phase images.
• Magnetic resonance-specific contrast agents are now available for hepatic imaging. • Hepatocellular adenomas enhance with gadoxetic acid as in previous CT/MRI experience. • Enhancement during the hepatobiliary phase is less in HCAs than in liver. • Typical HCAs appear as hypointense lesions on T1-w hepatobiliary phase images. • True hyperintense HCA enhancement can occasionally occur during the hepatobiliary phase.
To assess the incremental value of hepatobiliary phase images in gadoxetate disodium-enhanced magnetic resonance imaging (MRI), and to compare diagnostic accuracy and lesion conspicuity on 10- and 20-minute delayed images for preoperative detection of hepatic metastases with subgroup analysis according to size and history of chemotherapy.
Forty-six patients with 107 metastases who underwent surgery after gadoxetate disodium-enhanced MRI were evaluated. Four observers independently interpreted three sets: dynamic set comprising precontrast T1-, T2-weighted, and dynamic images; 10-minute set comprising dynamic set and 10-minute delayed; 20-minute set comprising 10-minute set and 20-minute delayed. Diagnostic accuracy was compared with subgroup analysis. Liver-to-lesion signal ratio (SR) was calculated using the region of interest method and compared.
Mean A(z) and sensitivities were significantly higher for 10- (A(z) = 0.894, sensitivity = 95.6%) and 20-minute (0.910, 97.2%) than dynamic set (0.813, 79.9%) (P < 0.001), with no significant difference between 10- and 20-minute sets (P = 0.140). In patients with small (≤1 cm) metastases and a history of chemotherapy, sensitivities were significantly higher with 10- (88.2%) and 20-minute (91.6%) sets than dynamic set (48.6%) (P < 0.001). SR was significantly higher for 10- and 20-minute delayed than precontrast and dynamic, with significantly higher SR on 20- than 10-minute delayed.
Regardless of size or prior chemotherapy, detection of hepatic metastases was significantly improved by adding hepatobiliary phase images without significant differences between 10- and 20-minute delayed.
To compare the diagnostic accuracy of contrast-enhanced computed tomography (CE-CT), contrast-enhanced ultrasonography (CE-US), superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), and gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in the evaluation of colorectal hepatic metastases.
In all, 111 patients with colorectal cancers were enrolled in this study. Of the 112 metastases identified in 46 patients, 31 in 18 patients were confirmed histologically and the remaining 81 in 28 patients were confirmed by follow-up imaging. CE-CT, CE-US, SPIO-MRI, and Gd-EOB-MRI were evaluated. Mean (of three readers, except for CE-US) area under the receiver operating characteristic curve (A(z) ), sensitivities, and positive predictive values (PPV) were calculated. Each value was compared to the others by variance z-test or chi-square test with Bonferroni correction.
For all lesions, mean A(z) and sensitivity of Gd-EOB-MRI (0.992, 95% [56/59]) were significantly greater than those of CE-CT (0.847, 63% [71/112]) and CE-US (0.844, 73% [77/106]). For lesions ≤1 cm, mean A(z) and sensitivity of Gd-EOB-MRI (0.999, 92% [22/24]) were significantly greater than those of CE-CT (0.685, 26% [13/50]) and CE-US (0.7, 41% [18/44]). Mean A(z) (95% CI) of SPIO-MRI for all lesions (0.966 [0.929-0.987]) and lesions ≤ 1 cm (0.961 [0.911-0.988]) were significantly greater than those of CE-CT and CE-US. Mean sensitivity of SPIO-MRI for lesions ≤1 cm (63%, 26/41) was significantly greater than that of CE-CT.
Gd-EOB-MRI and SPIO-MRI were more accurate than CE-CT and CE-US for evaluation of liver metastasis in patients with colorectal carcinoma.
A hepatocyte-specific contrast agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), was approved in Japan in 2008. This contrast agent enhances the blood pool and also is hepatocyte specific: it is taken up by hepatocytes and excreted into the biliary tract. Approximately 50% of the administered dose of Gd-EOB-DTPA is taken up by normal hepatocytes and subsequently excreted into the biliary tract, while the remaining 50% is excreted via the kidney. Hepatocellular uptake is considered to represent passive diffusion mediated by organic anion transporter polypeptide 1 (OATP1), which is expressed on the hepatocyte membrane. Gd-EOB-DTPA-enhanced MRI may offer a breakthrough for the diagnosis of liver tumors, particularly early hepatocellular carcinoma (HCC). The differentiation of dysplastic nodules from early HCC has remained difficult, even for pathologists specialized in liver tumors, but Gd-EOB-DTPA MRI facilitates an objective diagnosis with accuracy close to that of HCC-specialized pathologists. In conclusion, Gd-EOB-DTPA MRI facilitates the diagnosis of hypervascular advanced HCC and the differentiation of early HCC and dysplastic nodules, which used to be difficult, even with CT during arterial portography, and offers a high accuracy rate. Thus, Gd-EOB-DTPA MRI will have a significant impact on diagnostic algorithm for HCC.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The majority of HCCs develop in cirrhotic livers, and the early detection and characterization of this entity is very important. Pathologically, human HCC develops in a multistep fashion in the following sequence: from low-grade dysplastic nodule (LGDN), to high-grade dysplastic nodule (HGDN), early HCC, well-differentiated HCC, nodule-in-nodule HCC, and, finally, to moderately differentiated HCC. Differentiation between early HCC and DN is the most important issue in the clinical setting. CT during hepatic angiography (CTHA) and CT during arterial portography (CTAP) are the most sensitive tools in the differentiation of premalignant/borderline lesions (LGDN and HGDN) and early HCC. Recent progress in imaging modality, especially Sonazoidenhanced US and Gd-EOB-DTPA MRI, is starting to play a very important role in the imaging of multistep hepatocarcinogenesis, resulting in changing the therapeutic strategy of these nodular lesions associated with liver cirrhosis.
To intraindividually compare gadoxetic acid-enhanced magnetic resonance (MR) imaging with contrast material-enhanced multi-detector row computed tomography (CT) in detection of pancreatic carcinoma and liver metastases.
The ethics committee approved this retrospective study with waiver of informed consent. This study included 100 patients (53 men, 47 women; mean age, 67.8 years) consisting of 54 patients with pathologically confirmed pancreatic carcinoma (mean size, 33 mm) and 46 without a pancreatic lesion. Sixty-two liver metastases (mean size, 10 mm) in 15 patients with pancreatic carcinoma were diagnosed at pathologic examination or multimodality assessment. Three readers blinded to the final diagnosis interpreted all MR (precontrast T1- and T2-weighted and gadoxetic acid-enhanced dynamic and hepatocyte phase MR images) and tetraphasic dynamic contrast-enhanced CT images and graded the presence (or absence) of pancreatic carcinoma and liver metastasis on patient-by-patient and lesion-by-lesion bases. Receiver operating characteristic analysis, McNemar test, and Fisher test were performed to compare the diagnostic performance of CT and MR imaging.
No significant differences were observed between CT and MR images in depiction of pancreatic carcinoma. However, MR imaging had greater sensitivity in depicting liver metastasis than did CT for two of the three readers in the MR imaging-versus-CT analysis (85% vs 69%, P = .046) and for all three readers in the lesion-by-lesion analysis (92%-94% vs 74%-76%, P = .030-.044).
Gadoxetic acid-enhanced MR imaging was equivalent to dynamic contrast-enhanced CT in depicting pancreatic carcinoma and had better sensitivity for depicting liver metastases, suggesting the usefulness of gadoxetic acid-enhanced MR imaging for evaluation of patients with pancreatic carcinoma.
To assess the value of hepatobiliary phase gadoxetic acid (EOB)-enhanced magnetic resonance imaging (MRI) for the diagnosis of early stage hepatocellular carcinoma (HCC) (<3 cm) compared to triple-phase dynamic multidetector computed tomography (MDCT).
In all, 52 patients with 60 pathologically proven HCCs underwent both EOB-enhanced MRI and triple-phase dynamic MDCT. Two radiologists independently and blindly reviewed three image sets: 1) MDCT, 2) dynamic MRI (unenhanced and EOB-enhanced dynamic MR images), and 3) combined MRI (dynamic MRI + hepatobiliary phase images) using a five-point rating scale on a lesion-by-lesion basis. Receiver operating characteristics (ROC) analysis was performed, and sensitivity and specificity were calculated.
The area under the ROC curve (Az) of dynamic MRI was equivalent to that of MDCT for both readers. For both readers, Az and sensitivity of combined MRI for smaller lesions (<1.5 cm) were significantly higher than that of dynamic MRI and MDCT (P < 0.0166). The majority of false-negative nodules on dynamic MRI or MDCT (75% and 62%, respectively) were due to a lack of identified washout findings.
Hepatobiliary phase images can increase the value of EOB-enhanced MRI in the diagnosis of early stage HCC. The sensitivity and accuracy were significantly superior to MDCT for the diagnosis of lesions less than 1.5 cm.
The purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on contrast-enhanced MR imaging (CE-MRI) obtained with Gd-EOB-DTPA.
A total of 99 patients with cirrhotic liver (n=58; Child-Pugh class A, n=30; B, n=22; C, n=6) and normal liver (n=41) underwent Gd-EOB-DTPA-enhanced MR imaging. CE images were obtained before contrast injection, in the arterial phase (AP) at 25s or modified scan delay, in the portal phase (PP) at 70s, in the equilibrium phase (EP) at 3 min, and in the hepatobiliary phase (HP) at 3 times (10, 15 and 20 min). Signal intensity of the liver in all phases was defined using region-of-interest measurements for relative enhancement (RE) calculation.
In normal-liver and Child-Pugh class A and B patients, mean RE of liver parenchyma increased significantly (P<0.03-0.001) with time until 20-min HP. Conversely, mean RE for Child-Pugh class C patients did not show any increasing tendency after PP. Mean RE of liver parenchyma at EP and HP (10-, 15- and 20-min) was highest in normal liver, followed by Child-Pugh class A, B and C cirrhosis (P<0.02-0.001).
Hepatic parenchymal enhancement on CE-MR images obtained using Gd-EOB-DTPA is affected by the severity of cirrhosis.
To prospectively assess the additional value of the hepatobiliary (HB) phase of Gd-EOB-DTPA-MRI in identifying and characterising small (≤ 2 cm) hepatocellular carcinomas (HCCs) undetermined in dynamic phases alone because of their atypical features, according to the AASLD criteria.
127 cirrhotic patients were evaluated with Gd-EOB-DTPA-MRI in two sets: unenhanced and dynamic phases; unenhanced, dynamic and HB phases. Sixty-two out of 215 nodules (29%) were atypical in 42 patients (33%).
62 atypical nodules were reported at histology: high-grade dysplastic nodules (HGDN)/early HCC (n = 20), low-grade DN (LGDN) (n = 21), regenerative nodules (n = 17) and nodular regenerative hyperplasia (n = 4). The sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV) were increased by the addition of the HB phase: 88.4-99.4%, 88-95%, 88-98.5%, 97-99%, and 65-97.5%, respectively. Twenty atypical nodules were malignant (32%), 19 of which were characterised only during the HB phase.
The HB phase is 11% more sensitive in the classification of HGDN/early HCC than dynamic MRI, with an added value of 32.5% in the NPV. The high incidence (33%) of atypical nodules and their frequent malignancy (32%) suggest the widespread employment of Gd-EOB-DTPA-MRI in the follow-up of small nodules (≤ 2 cm) in cirrhosis.
To evaluate the effect of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) for the diagnosis of hepatocellular carcinoma (HCC).
The phantom signal intensity was measured. We also evaluated 72 patients including 30 patients with HCC. T2WI and DWI were obtained before and then 4 and 20 min after injecting the contrast medium. The signal to noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) were calculated in the tumor and liver parenchyma.
The phantom signal intensity increased on T2WI at a concentration of contrast medium less than 0.2 mmol/L but decreased when the concentration exceeded 0.4 mmol/L. SNR of the liver parenchyma on T2WI was significantly different between before and 4 min after injecting the contrast medium, while there were no significant differences between before and 4 and 20 min after injection. On T2WI, SNR, and CNR of HCC showed no significant differences at any time. SNR, CNR, and ADC of the liver parenchyma and tumor on DWI also showed no significant differences at any time.
It is acceptable to perform T2WI and DWI after injection of Gd-EOB-DTPA for the diagnosis of HCC.
To compare the accuracy of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI with that of diffusion-weighted MRI (DWI) in the detection of small hepatic metastases (2 cm or smaller).
Forty-five patients underwent abdominal MRI at 3 T, including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), heavily T2WI (HASTE), DWI with a b-value of 500 s/mm(2) and contrast-enhanced MRI with Gd-EOB-DTPA. Two groups were assigned and compared: group A (T1WI, T2WI, HASTE and contrast-enhanced study with Gd-EOB-DTPA), and group B (T1WI, T2WI, HASTE and DWI). Two observers independently interpreted the images obtained in a random order. For all hepatic metastases, the diagnostic performance using each imaging set was evaluated by receiver-operating characteristic (ROC) curve analysis.
A total of 51 hepatic metastases were confirmed. The area under the ROC curve (Az) of group A was larger than that of group B, and the difference in the mean Az values between the two image sets was statistically significant, whereas, there were three metastases that lay near thin vessels or among multiple cysts and were better visualised in group B than in group A.
Gd-EOB-DTPA-enhanced MRI showed higher accuracy in the detection of small metastases than DWI.
To investigate the mechanism of enhancement of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced hepatobiliary phase magnetic resonance (MR) images and to characterize HCC thus enhanced.
This retrospective study was approved by the institutional review board, and patient informed consent for research use of the resected specimen was obtained. MR images in 25 patients (20 men, five women; mean age, 68 years; range, 49-82 years) with 27 resected hypervascular HCCs (one well, 13 moderately, 13 poorly differentiated) that demonstrated hepatocyte-selective enhancement on gadoxetic acid-enhanced MR images, were quantitatively studied, and findings were correlated with results of immunohistochemical staining for a sinusoidal transporter, organic anion transporting polypeptide (OATP) 1B1 (OATP1B1) and/or OATP1B3 (OATP1B1 and/or -1B3), and a canalicular transporter, multidrug resistance-associated protein 2 (MRP2), and also with bile accumulation in tumors. Statistical analysis was performed with the Student t test and Scheffé post hoc test.
Combined with positive OATP1B1 and/or -1B3 expression (O+), two patterns of MRP2 expression contributed to high enhancement: decreased expression (M-, n = 3) and increased expression at the luminal membrane of pseudoglands (M+[P], n = 3). Nodules without OATP1B1 and/or -1B3 expression (O-, n = 13) and nodules with O+ associated with increased MRP2 expression only at the canaliculi (M+[C], n = 8) induced significantly lower enhancement than those with the two expression patterns described before (O+/M- group vs O- group, P = .002; O+/M- group vs O+/M+[C] group, P = .047; O+/M+[P] group vs O- group, P < .001; O+/M+[P] group vs O+/M+[C] group, P < .001). Nodules with bile pigment (n = 12) showed significantly higher enhancement (P = .004); all five nodules (one well differentiated HCC, four moderately differentiated HCCs), which were enhanced more than adjacent liver parenchyma, contained bile pigment.
High hepatocyte-selective enhancement is induced by expression patterns of transporters, which may result in accumulation of gadoxetic acid in cytoplasm of tumor cells or in lumina of pseudoglands. An HCC with gadoxetic acid enhancement is characterized by bile accumulation in tumors.
To evaluate the effect of liver function on liver signal intensity in gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in humans and to examine the biochemical factors related to signal intensity in the hepatobiliary phase.
This study included 48 patients with suspected hepatocellular carcinoma or metachronous liver metastases from colorectal cancer. The patients were divided into 2 groups: the chronic liver dysfunction and the normal liver function. All the individuals of both groups had magnetic resonance imaging before injection and at 5, 10, 15, 20, 25, and 30 minutes after bolus administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. The time point when the mean liver signal-to-noise ratio (SNR) reached a peak was determined for each group, and the mean liver SNR at the peak point was compared between the groups. In all the patients, stepwise multivariate analysis was used to evaluate the relationship between the liver SNR at the peak time point and the laboratory data, using the following biochemical factors: prothrombin time, total bilirubin level, cholinesterase level, albumin level, creatinine level, indocyanine green retention rate at 15 minutes, and Child-Pugh score.
The mean values of liver SNR increased gradually. The mean liver SNR reached peak at 30 minutes after contrast injection in both groups and was significantly lower in the chronic liver dysfunction group than in the normal liver function group. Indocyanine green retention rate at 15 minutes was the only significant contributor to the liver signal intensity at the peak time point (30 minutes).
The degree of liver enhancement in the hepatobiliary phase may reflect liver cell function. The measurement of liver signal intensity in the hepatobiliary phase may be useful in predicting whole and regional hepatic functional reserves.
To retrospectively investigate enhancement patterns of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI in relation to histological grading and portal blood flow.
Sixty-nine consecutive patients with 83 histologically proven HCCs and DNs were studied. To assess Gd-EOB-DTPA uptake, we calculated the EOB enhancement ratio, which is the ratio of the relative intensity of tumorous lesion to surrounding nontumorous area on hepatobiliary phase images (post-contrast EOB ratio) to that on unenhanced images (pre-contrast EOB ratio). Portal blood flow was evaluated by CT during arterial portography.
Post-contrast EOB ratios significantly decreased as the degree of differentiation declined in DNs (1.00 ± 0.14) and well, moderately and poorly differentiated HCCs (0.79 ± 0.19, 0.60 ± 0.27, 0.49 ± 0.10 respectively). Gd-EOB-DTPA uptake, assessed by EOB enhancement ratios, deceased slightly in DNs and still more in HCCs, while there was no statistical difference in the decrease between different histological grades of HCC. Reductions in portal blood flow were observed less frequently than decreases in Gd-EOB-DTPA uptake in DNs and well-differentiated HCCs.
Reduced Gd-EOB-DTPA uptake might be an early event of hepatocarcinogenesis, preceding portal blood flow reduction. The hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI may help estimate histological grading, although difficulties exist in differentiating HCCs from DNs.
Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) represent the most frequent non-vascular benign liver tumors. They are often asymptomatic. The widespread use of high-resolution imaging modalities leads to an increase of incidental detection of FNH and HA. Physicians are thus increasingly confronted with these formerly rarely recognized conditions, stressing the need for concise but adequate information on the optimal clinical strategies for these patients. FNH is the most common non-vascular benign tumor of the liver. It probably arises as a polyclonal, hyperplastic response to a locally disturbed blood flow. It is typically found in asymptomatic women. Histologically, FNH can be described as a focal form of cirrhosis. Complications of FNH are extremely rare and surgical resection is generally not advised. HA is a rare monoclonal, but benign liver tumor primarily found in young females using estrogen-containing contraceptives. Although its exact etiology is unknown, a direct link between sex steroid exposure and the uncontrolled hepatocellular growth is suspected. Complications of HA are spontaneous bleeding and malignant transformation. Withdrawal of estrogen treatment and excision of large tumors (>5 cm) are established therapeutic strategies. In conclusion, although FNH and HA are reasonably well-described clinical and histopathological entities, their epidemiology and pathophysiology need to be further unraveled.
Diffusion-weighted MR imaging is increasingly applied to detect and characterize focal hepatic lesions. In this update article, technical aspects regarding diffusion-weighted echo-planar imaging (DW-EPI) of the liver will be addressed, and concepts for image interpretation will be provided. The value of DW-EPI for the detection of hepatic metastases is illustrated on the basis of a review of the literature and our personal experience. In this respect, special emphasis is given to the comparison of DW-EPI with well-established MR imaging techniques such as T2-weighted and contrast-enhanced MR imaging, and advantages and limitations of DW-EPI will be described. Based on the review, it is concluded that DW-EPI is more sensitive than T2-weighted MR imaging and at least as accurate as superparamagnetic iron oxide-enhanced or gadolinium-enhanced MR imaging for the detection of hepatic metastases. Although difficulties occasionally arise in further characterizing small lesions detected with DW-EPI, substantial improvements in the preoperative evaluation of liver metastases in candidates for hepatic resection may be expected.
Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a new hepatobiliary magnetic resonance imaging (MRI) contrast agent with a dual elimination: 70% via the liver and bile and 30% via the kidney in normal rats. The abdominal enhancement patterns of this new compound and the uptake mechanism by the liver were studied in rats using tissue relaxometry and MRI.
Twelve normal rats, 33 rats treated with agents designed to inhibit biliary excretion of the agent, and 6 rats with surgically ligated common bile ducts received Gd-EOB-DTPA intravenously. Distribution and excretion were measured by MR relaxometry. MR signal intensity was measured over time for liver, kidney, and bowel.
In normal animals, 0.1 mmol/kg Gd-EOB-DTPA induced a significantly greater (200%) and more prolonged liver signal enhancement (100% at 30 minutes) than Gd-DTPA at the same dose. Either hyperbilirubinemia, induced by common bile duct ligation, or bromosulfophtalein (BSP) infusion inhibited liver uptake of Gd-EOB-DTPA, resulting in a preferential elimination via the kidney. Taurocholate (TC), an inhibitor of the bile acid transporter, was unable to block the liver uptake of Gd-EOB-DTPA. Blood half-lives of Gd-EOB-DTPA in rats were 2.4 minutes for the first component and 8.2 minutes for the second.
Data indicate that transport of Gd-EOB-DTPA through the liver into bile is driven by the organic anion transporter. The relation between enhancement of liver and kidney may be diagnostically useful to indirectly evaluate liver excretory function. Yet, persistent enhancement of liver, even in the presence of severe hyperbilirubinemia, should be sufficient to identify focal mass lesions.
Gadolinium (4s)-4-(4-ethoxybenzyl-3,6,9-tris(carboxylato-methyl)-3,6,9- triazaudecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocellular-directed magnetic resonance (MR) contrast agent, and coated superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared for uptake and enhancement in a rodent model of radiation-induced liver injury. A single x-irradiation exposure (50-70 Gy) was delivered to one side of the liver in 18 rats. MR imaging was performed 3 days after x irradiation with sequential injections of the two contrast agents in the same rats. Additionally, biliary excretion of Gd-EOB-DTPA was quantified after whole-liver irradiation in five rats. Electron microscopy of the irradiated liver demonstrated mitochondrial injury in both hepatocyte and Kupffer cell populations. With Gd-EOB-DTPA, however, liver enhancement and biliary excretion were not affected by irradiation. Uptake of SPIO was decreased in the irradiated portion of the liver, with a precise demarcation between irradiated and nonirradiated zones at MR imaging.
Gadolinium diethylenetriaminepentaacetic acid (DTPA) covalently linked to the lipophilic ethoxybenzyl moiety (Gd-EOB-DTPA) was designed for use as a contrast agent in hepatobiliary magnetic resonance imaging. With T1 relaxivity values of 8.7 L/mmol.second in plasma and 16.6 L/mmol.second in rat liver tissue and a median lethal dose of 10 mmol/kg when administered intravenously in mice and rats, Gd-EOB-DTPA has a fairly high margin of safety. In rats and monkeys, biodistribution studies performed 7 days after administration of 0.25 mmol/kg revealed very little retention of gadolinium (less than 1%) in the tissues, indicating complete elimination via renal and biliary excretion. Biliary excretion was inhibited by coadministration of sulfobromophthalein, indicating the involvement of a carrier-mediated transport system based on the enzyme glutathione-S-transferase. In rats, the biliary transport maximum was 5 mumol gadolinium/min.kg. High T1 relaxivity of Gd-EOB-DTPA in rat liver in vivo can be explained by transient interaction with intracellular components and by increased microviscosity inside the hepatocyte.
Gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9- triazaundecandioic acid-disodium salt (EOB-DTPA) ethoxybenzyl is a new hepatobiliary magnetic resonance (MR) contrast agent with dual elimination: 75% through the liver and bile and 25% through the kidneys in normal rats. In this study, Gd-EOB-DTPA was evaluated in a rodent model of metastatic liver disease to measure both relative enhancement and lesion-to-liver contrast. A secondary goal was to compare the relative performance of spin-echo (SE) and short inversion time inversion-recovery (STIR) imaging to demonstrate enhancement with Gd-EOB-DTPA. After administration of 0.1 mmol of Gd-EOB-DTPA per kilogram, liver signal increased (positive enhancement) more than 200% with the use of the SE technique and declined (negative enhancement) by more than 80% with use of the STIR technique. Only minimal enhancement of implanted liver tumor was observed. Unlike the tumor, the gall-bladder and lumen of the duodenum were progressively enhanced over time. The lesion-to-liver contrast increased by approximately 500% with both the SE and STIR techniques after administration of Gd-EOB-DTPA.
Gd-Ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a highly water-soluble paramagnetic contrast agent. Due to its protein binding of about 10% and its lipophilic residue, Gd-EOB-DTPA exhibits both renal (30% of the dose) and hepatobiliary (70%) excretion in rats. Despite its lipophilic character, the compound displays a low toxicity (LD50 = 7.5 mmol/kg). T1-relaxivity of 5.3 liters mmol-1 s-1 in water, 8.7 liters mmol-1 s-1 in plasma, and 16.9 liters mmol-1 s-1 in rat liver together with the hepatocellular uptake explain the liver-specific contrast enhancement of Gd-EOB-DTPA. The diagnostic dose is considerably lower than the amount of Magnevist used in abdominal imaging. The preclinical studies suggest its clinical role as being a hepatobiliary contrast agent for MRI.