Liver-specific Contrast Agent Research Articles

Gadoxetate disodium (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging for differentiation between benign and malignant splenic lesions in dogs.

Malignant splenic lesions in dogs are common, with hemangiosarcoma diagnosed most frequently, and there have been no consistent clinicopathologic, gross, or imaging characteristics identified that differentiate malignant from benign splenic lesions. Histopathology is required for definitive diagnosis, and given the poor long-term prognosis of malignant splenic lesions, a noninvasive tool to aid in diagnosis would be valuable. This prospective cohort study utilized gadoxetate disodium, a liver-specific contrast agent (Gd-EOB-DPTA; Eovist), to identify the general lesion and pre- and postcontrast signal characteristics of benign and malignant splenic and hepatic lesions in dogs with naturally occurring disease. Twenty-five dogs were enrolled, Eovist-enhanced MRI was performed, and dogs were taken to surgery for splenectomy and other organ biopsy. All histopathology and MRI studies were evaluated by a single pathologist and a single radiologist, respectively. The associations between the tumor type and numerous variables defined on MRI were evaluated using Fisher's exact tests, and the significance was identified at a P-value of.05. Malignant splenic masses were identified in 11/25 (44%) dogs, and 5/11 malignancies represented hemangiosarcoma. The presence of abdominal effusion (P=.017) and the presence of hepatic nodules on MRI (P=.009) were associated with splenic malignancy. There were no benign T2 hyperintense and no malignant T2 hypointense lesions (P=.021). Utilization of the T2 W MRI sequence may aid in the identification of malignant splenic lesions, particularly when accompanied by abdominal effusion and hepatic lesions.

Trapped in Endosome PEGylated Ultra-Small Iron Oxide Nanoparticles Enable Extraordinarily High MR Imaging Contrast for Hepatocellular Carcinomas.

The early diagnosis of hepatocellular carcinomas (HCCs) remains challenging in the clinic. Primovist-enhanced magnetic resonance imaging (MRI) aids HCC diagnosis but loses sensitivity for tumors <2cm. Therefore, developing advanced MRI contrast agents is imperative for improving the diagnostic accuracy of HCCs in very-early-stage. To address this challenge, PEGylated ultra-small iron oxide nanoparticles (PUSIONPs) are synthesized and employed as liver-specific T1 MRI contrast agents. Intravenous delivery produces simultaneous hyperintense HCC and hypointense hepatic parenchyma signals on T1 imaging, creating an extraordinarily high tumor-to-liver contrast. Systematic studies uncover PUSIONP distribution in hepatic parenchyma, HCC lesions at the organ, tissue, cellular, and subcellular levels, revealing endosomal confinement of PUSIONP without aggregation. By mimicking such situations, the dependency of relaxometric properties on local PUSIONP concentration is investigated, emphasizing the key role of different endosomal concentrations in liver and tumor cells for high tumor-to-liver contrast and clear tumor boundaries. These findings offer exceptional imaging capabilities for early HCC diagnosis, potentially benefiting real HCC patients.

Multiparametric MRI in hepatocellular carcinoma, part2 : Diffusion-weighted imaging in the primary diagnostics and treatment monitoring

In addition to morphology and tissue perfusion, diffusion-weighted imaging (DWI) is the third pillar of multiparametric diagnostics in oncology. Due to the strong correlation between the apparent diffusion coefficient (ADC) and cell count in hepatocellular carcinoma (HCC), it can be used as asurrogate marker for tumor cell quantity. Therefore, ADC effectively reflects the effects of cytoreductive treatment, such as transarterial chemoembolization (TACE) and systemic chemotherapy and becomes an important clinical marker for treatment response. The DWI should remain an integral part of a magnetic resonance imaging (MRI) protocol in primary HCC diagnostics and treatment monitoring but is of secondary clinical importance compared to contrast-enhanced MRI perfusion sequences and the use of liver-specific contrast agents. For the future, standardization of DWI sequences for better comparability of various study protocols would be desirable.

Preparation and performance of biocompatible gadolinium polymer as liver-targeting magnetic resonance imaging contrast agent

A biocompatible macromolecule-conjugated gadolinium chelate complex (PAV2-EDA-DOTA-Gd) as a new liver-specific contrast agent for magnetic resonance imaging (MRI) was synthesized and evaluated. An aspartic acid-valine copolymer was used as a carrier and ethylenediamine as a chemical linker, and the aspartic acid-valine copolymer was covalently linked to the small molecule MRI contrast agent Gd-DOTA (Dotarem) to synthesize a large molecule contrast agent. Invitro MR relaxation showed that the T1-relaxivity of PAV2-EDA-DOTA-Gd (13.7mmol-1Ls-1) was much higher than that of the small-molecule Gd-DOTA (4.9mmol-1Ls-1). Invivo imaging of rats showed that the enhancement effect of PAV2-EDA-DOTA-Gd (55.37 ± 2.80%) on liver imaging was 2.6 times that of Gd-DOTA (21.12 ± 3.86%), and it produced a longer imaging window time (40-70min for PAV2-EDA-DOTA-Gd and 10-30min for Gd-DOTA). Preliminary safety experiments, such as cell experiments and tissue sectioning, showed that PAV2-EDA-DOTA-Gd had low toxicity and satisfactory biocompatibility. The results of this study indicated that PAV2-EDA-DOTA-Gd had high potential as a liver-specific MRI contrast agent.

Comparison of the Ability of Gadobenate Dimeglumine and Gadolinium Ethoxybenzyl Dimeglumine to Display the major Features for Noninvasively Diagnosing Hepatocellular Carcinoma According to the LI-RADS 2018v.

To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.

Application of liver-specific contrast agents for evaluation of focal liver lesions - Expert recommendations from the Gastrointestinal and Abdominal Imaging Workgroup of the German Roentgen Society.

Contrast-enhanced MRI is the imaging modality of choice for the detection and differential diagnosis of focal liver lesions. Liver-specific contrast agents (CAs) are now well established in addition to extracellular contrast agents. However, there is a lack of explicit recommendations reflecting the pros and cons of each specific contrast agent in the daily routine. Development of recommendations for the clinical application of liver-specific CAs by members of the Gastrointestinal and Abdominal Imaging Workgroup within the Germany Radiological Society, using methodology comparable to that of an S1 guideline with informal consensus. The diagnostic criteria for the evaluation of liver lesions are intentionally outside the scope of this article, as there are already plenty of excellent publications available. The application of liver-specific CAs in the daily routine is associated with advantages and disadvantages due to the specific pharmacokinetic and pharmacodynamic properties and necessitates adjustment of the imaging technique as well consideration during image interpretation. Recommendations for the application of liver-specific CAs are presented based on different clinical scenarios, taking into account current evidence and guidelines. · Both liver-specific and extracellular contrast agents are established. · Liver-specific contrast agents make it possible to draw conclusions about the hepatocellular function of a lesion. · Recommendations for the use of liver-specific contrast agents in the daily routine are presented. · Ringe KI, Fischbach F, Grenacher L et al. Einsatz leberspezifischer Kontrastmittel in der MRT zur Beurteilung von Leberläsionen - Expertenempfehlungen der AG Gastrointestinal- und Abdominaldiagnostik der Deutschen Röntgengesellschaft. Fortschr Röntgenstr 2023; DOI: 10.1055/a-2192-9921.

Adaptive Training: A New Method to Improve the Image Quality of Abdominal Magnetic Resonance Imaging.

In abdominal magnetic resonance imaging (MRI), the late hepatic arterial phase is particularly important for the diagnosis of hepatocellular carcinoma (HCC). However, poor patient compliance with breath-hold imaging acquisition protocols and the administration of the liverspecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) increases the motion artifacts that degrade the quality of the images making it more difficult to interpret the images. This study aimed to evaluate the role of adaptive respiratory training in improving the quality of the MRI by reducing the motion artifacts and improving the signal intensity from the regions of interest (ROI) in the late hepatic arterial phase. A total of 120 patients who underwent an abdominal MRI between 2021 to 2022 to assess for the liver disease were included in the study. These patients were divided into two groups: the experimental group and the control group. The patients in the experimental group received adaptive training. The incidence of motion artifacts and the signal intensity in the late hepatic arterial phase within the abdominal aorta, hepatic artery, splenic artery, and hepatic parenchyma between the experimental group and the control group were compared. The incidence of motion artifacts in the experimental group was significantly reduced by 28.3% (p = 0.001, Chi-square value = 12.079). In the late hepatic arterial phase, the signal intensity of the abdominal aorta, the hepatic artery, the splenic artery, and the hepatic parenchyma increased by 7.3%, 27.4%, 29.5%, and 6.9%, respectively. Adaptive respiratory training reduced the incidence of motion artifacts and improved the signal intensity for various ROI. The improved image quality could potentially facilitate image interpretation and reduce the number of repeat MRI scans.

FRI-493 - Safety and signal intensity of a novel liver-specific MRI contrast agent, Orviglance® (manganese chloride tetrahydrate), in adult subjects with mild, moderate, or severe hepatic impairment

FRI-493 - Safety and signal intensity of a novel liver-specific MRI contrast agent, Orviglance® (manganese chloride tetrahydrate), in adult subjects with mild, moderate, or severe hepatic impairment

Comparison of gadolinium-based contrast agents for MR cholangiography in saline, blood and bile: a phantom study

BackgroundWe compared T1- and T2-weighted signal intensities of liver-specific (gadoxetate, gadobenate) and non-specific (gadoterate) gadolinium contrast agents (CAs) in a bile phantom.MethodsIn a phantom study, gadoxetate, gadobenate, and gadoterate were diluted in saline, blood, and bile at different concentrations (0, 0.25, 0.5. 1, 2.5, 5, 10, and 25 mM) and imaged in a 3-T magnetic resonance imaging (MRI) system using T1- and T2-weighted sequences. The maximum signal intensities of CAs were compared for each sequence separately and across all T1-weighted sequences using one-way ANOVA.ResultsUsing T1-weighted sequences, CA concentration-dependent signal intensity increase was followed by decrease due to T2* effects. Comparing CAs for each sequence in bile yielded higher maximum signal intensities with gadobenate than gadoxetate and gadoterate using T1-weighted spin-echo (p < 0.010), multiecho gradient- and spin-echo (p < 0.001), and T1-weighted high-resolution isotropic volume excitation (eTHRIVE) sequences (p < 0.010). Comparing across all T1-weighted sequences in the bile phantom, gadobenate imaged using T1-weighted turbo field-echo (TFE) sequence showed the highest signal intensity, significantly higher than that using other CAs agents or sequences (p < 0.004) except for gadobenate and gadoxetate evaluated with three-dimensional multiecho fast field-echo (3D-mFFE) and gadoxetate with T1-weighted TFE sequence (p > 0.141). Signal reduction with CA concentration-dependent decrease was observed on T2-weighted images.ConclusionIn this bile phantom study of gadolinium-based CA, gadobenate and gadoxetate showed high signal intensity with T1-weighted TFE and 3D-mFFE sequences, which supports their potential utility for contrast-enhanced hepatobiliary MRI.Key points• Contrast-enhanced magnetic resonance (MR) cholangiography depends on contrast agent type, kinetics, and concentration in bile,• We compared signal intensities of three contrast agents in a bile phantom study.• Gadobenate, gadoxetate, and gadoterate demonstrated different signal intensities at identical concentrations.• Gadoxetate and gadobenate showed high signal intensities on T1-weighted MR sequences.

Manganese (II) Complex of 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid (NOTA) as a Hepatobiliary MRI Contrast Agent.

Magnetic resonance imaging (MRI) is increasingly used to diagnose focal and diffuse liver disorders. Despite their enhanced efficacy, liver-targeted gadolinium-based contrast agents (GBCAs) raise safety concerns owing to the release of toxic Gd3+ ions. A π-conjugated macrocyclic chelate, Mn-NOTA-NP, was designed and synthesized as a non-gadolinium alternative for liver-specific MRI. Mn-NOTA-NP exhibits an r1 relaxivity of 3.57 mM-1 s-1 in water and 9.01 mM-1 s-1 in saline containing human serum albumin at 3 T, which is significantly greater than the clinically utilized Mn2+-based hepatobiliary drug, Mn-DPDP (1.50 mM-1 s-1), and comparable with that of GBCAs. Furthermore, the in vivo biodistribution and MRI enhancement patterns of Mn-NOTA-NP were similar to those of the Gd3+-based hepatobiliary agent, Gd-DTPA-EOB. Additionally, a 0.05 mmol/kg dose of Mn-NOTA-NP facilitated high-sensitivity tumor detection with tumor signal enhancement in a liver tumor model. Ligand-docking simulations further indicated that Mn-NOTA-NP differed from other hepatobiliary agents in their interactions with several transporter systems. Collectively, we demonstrated that Mn-NOTA-NP could be a new liver-specific MRI contrast agent.

Imaging of Hepatobiliary Cancer

The liver and biliary tree are common sites of primary and secondary malignancies. MRI followed by CT is the mainstay for the imaging characterization of these malignancies with the dynamically acquired contrast enhanced phases being the most important for diagnosis. The liver imaging reporting and data system classification provides a useful framework for reporting lesions in patents with underlying cirrhosis or who are at high risk for developing hepatocellular carcinoma. Detection of metastases is improved with the use of liver specific MRI contrast agents and diffusion weighted sequences. Aside from hepatocellular carcinoma, which is often diagnosed noninvasively, other primary hepatobiliary tumors may require biopsy for definite diagnosis, especially when presenting with nonclassic imaging findings. In this review, we examine the imaging findings of common and less common hepatobiliary tumors.

Evaluation of clinical safety and diagnostic efficacy of domestic liver-specific magnetic resonance contrast agent (gadoxetate disodium)

Objective: To evaluate the clinical safety and diagnostic efficacy of domestic gadoxetate disodium (GdEOBDTPA). Methods: The imaging data from patients with space-occupying liver lesions who underwent GdEOBDTPA enhanced magnetic resonance examination at West China Hospital of Sichuan University between January 2020 and September 2020 were analyzed retrospectively. Clinical indicators were evaluated by the incidental condition of transient severe respiratory motion artifacts (TSM) in the arterial phase to assess the safety profile.The differences in quantitative and qualitative indicators for the risk factors of TSM in the arterial phase between the TSM group and the non-TSM group were compared by t-test and χ2 test. Observational indicators of the accuracy of diagnostic procedures: The 2018 version of the Liver Imaging Reporting and Data System (LI-RADS) was used to evaluate the main signs, auxiliary signs, and LR grades of lesions. Postoperative pathological findings were used as the gold standard for evaluating and diagnosing hepatocellular carcinoma (HCC). Simultaneously, the relative enhancement degree of the liver, the contrast between the lesion and the liver, and the cholangiography in the hepatobiliary phase were evaluated. The McNemar test was used to compare the differences in the diagnostic efficiency of physician 1 and physician 2 in the diagnosis of hepatocellular carcinoma according to the 2018 version of LI-RADS. Results: A total of 114 cases were included in this study. The incidence rate of TSM was 9.6% (11/114). Age [(53.8 ± 11.3) years vs. (55.4 ± 15.4) years, t = 0.465, P = 0.497], body weight [(65.8 ± 11.1) kg vs. (60.8 ± 7.6) kg, t = 1.468, P = 0.228], body mass index [(23.9 ± 3.1) kg/m(2) vs. (23.4 ± 3.0) kg/m(2), t = 0.171, P = 0.680], liver cirrhosis ratio (39 cases vs. 4 cases, χ (2) =1.776, P = 0.183), proportion of mild to moderate pleural effusion (32 cases vs. 4 cases, χ (2) = 0.000, P = 0.986), and proportion of mild to moderate ascites (47 cases vs. 5 cases χ (2) = 0.000, P = 0.991) had no statistically significant difference between the groups of non-TSM and TSM patients. According to the 2018 version of LI-RADS for the LR5 category, there was no statistically significant difference between the two physicians' HCC diagnoses in terms of sensitivity (91.4% vs.86.4%, χ (2) = 1.500, P = 0.219), specificity (72.7 % vs. 69.7%, χ (2) = 0.000, P = 1.000), positive predictive value (89.2% vs. 87.5%, χ (2) = 2.250, P = 0.125), negative predictive value (77.4% vs. 67.6%, χ (2) = 2.250, P = 0.125), and accuracy (86.0% vs. 81.6%, χ (2) = 0.131, P = 0.125). According to physicians 1 and 2 film review results, 91.2% (104/114) and 89.5% (102/114) of the contrast agent were discharged into the common bile duct or duodenum, respectively. In addition, 86.0% (98/114) of the patients had good liver enhancement, and 91.2% (104/114) of the lesions showed low signals relative to the liver background. Conclusion: Domestic gadoxetate disodium has a good clinical safety profile and diagnostic efficacy.

Optimized visualization of focal liver lesions and vascular structures in real-time T1-weighted gradient echo sequences for magnetic resonance-guided liver procedures.

This study aimed to determine the optimal sequence parameters of a real-time T1-weighted (T1w) gradient echo (GRE) sequence for magnetic resonance (MR)-guided liver interventions. We included 94 patients who underwent diagnostic liver MR imaging (MRI) and acquired additional real-time T1w GRE sequences with a closed 1.5-T MRI scanner 20 min after a liver-specific contrast agent was injected. In four measurement series, one of the following four sequence parameters was changed, and repeated scans with different values for this parameter were acquired: flip angle (FA) (10-90°), repetition time (TR) (5.47-8.58 ms), bandwidth (BW) (300-700 Hz/pixel), and matrix (96 × 96-256 × 256). Two readers rated the visualizations of the target and risk structures (7-point Likert scale) and the extent of artifacts (6-point Likert scale); they also quantified the lesion-liver contrast ratio, the lesion-liver contrast-to-noise ratio (CNR), and the liver signal-to-noise ratio (SNR). Substratification analyses were performed for differences in overall visual and quantitative assessments depending on the lesion size, type, and the presence of cirrhosis. For the utilized FAs and matrix sizes, significant differences were found in the visual assessments of the conspicuity of target lesions, risk structures, and the extent of artifacts as well as in the quantitative assessments of lesion-liver contrast ratios and liver SNRs (all P < 0.001). No differences were observed for modified TR and BW. Significantly increased conspicuity of the target and vascular structures was observed for both higher FAs and matrix sizes, while the ghosting artifacts increased and decreased, respectively. For primary liver tumors compared with metastatic lesions, and for cirrhotic livers compared with normal liver parenchyma, significantly decreased conspicuity of the target lesions (P = 0.005, P = 0.005), lesion-liver CNRs (P = 0.005, P = 0.032), and lesion-liver contrast ratios (P = 0.015, P = 0.032) were found. All results showed no significant correlation with lesion size. We recommend an FA of 30°-45° and a matrix size of 128 × 128-192 × 192 for MR-guided liver interventions with real-time T1w sequences to provide a balance between good visualizations of target and risk structures, high signal intensities, and low ghosting artifacts. The visualization of the target lesion may vary due to clinical conditions, such as lesion type or associated chronic liver disease.

Diagnostic Possibilities of Magnetic Resonance Cholangiography with Intravenous Contrast in Diseases of the Bile Ducts

Every year the number of operations on the hepatobiliary zone is steadily increasing due to diseases of the bile ducts. Against this background, there is a need for an accurate diagnosis of complications of these interventions; classical magnetic resonance cholangiopancreatography (MRCP) is of limited use. With the introduction of a liver-specific contrast agent (Gd-EOB-DTPA), the possibility of diagnosing diseases of the bile ducts has expanded. In this clinical review, we review the technical aspects and benefits of Gd-EOB-DTPA-enhanced MR cholangiography. Various types of contrast agents, methods of their use in MRI, the dependence of the signal intensity in the bile ducts on the time of administration of the substance, the presence of chronic liver diseases are covered in detail. Separately, studies are given on the diagnosis of diseases of the bile ducts with altered biliary anatomy, biliary fistulas after surgical interventions. In conclusion, data are presented on promising studies of the functional state of the liver based on the use of MRI with hepatotropic contrast enhancement.

A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging.

Hepatobiliary magnetic resonance imaging (MRI) can inform the diagnosis of liver tumours in patients with liver cirrhosis and hepatitis. However, its clinical utility has been hampered by the lack of sensitive and specific contrast agents, partly because hepatocyte-specific nanoparticles, regardless of their surface ligands, are readily sequestered by Kupffer cells. Here we show, in rabbits, pigs and macaques, that the performance of hepatobiliary MRI can be enhanced by an ultrasmall nanoparticle composed of a manganese ferrite core (3 nm in diameter) and poly(ethylene glycol)-ethoxy-benzyl surface ligands binding to hepatocyte-specific transmembrane metal and anion transporters. The nanoparticle facilitated faster, more sensitive and higher-resolution hepatobiliary MRI than the clinically used contrast agent gadoxetate disodium, a substantial enhancement in the detection rate (92% versus 48%) of early-stage liver tumours in rabbits, and a more accurate assessment of biliary obstruction in macaques. The nanoparticle's performance and biocompatibility support the further translational development of liver-specific MRI contrast agents.

An activatable Mn(II) MRI probe for detecting peroxidase activity in vitro and in vivo

Myeloperoxidase (MPO), a hallmark of the function and activation of innate immune cells, can act as a ‘double-edged sword’, contributing to clear infection as well as causing tissue oxidizing damage in various inflammatory diseases. In this study, an activatable Mn(II) chelate-based magnetic resonance imaging (MRI) contrast agent (CA), Mn-TyEDTA (TyEDTA = tyrosine derived ethylenediaminetetraacetic acid) structurally featuring a phenol group as the electron-donor, was developed to sense the activity of peroxidase in vitro and in vivo. Mn-TyEDTA demonstrated a peroxidase activity-dependent relaxivity in the presence of horseradish peroxidase (HRP)/H2O2 with more than a 2.6-fold increase in water proton relaxivity produced (HRP, 500 U; H2O2, 4.5 eq). A mechanism of peroxidase-mediated Mn(II) monomer radical polymerization was confirmed with those oligomers of Mn-TyEDTA such as dimer, trimer and tetramer were found in the LC-MS study. Dynamic MR imaging of normal mice revealed rapid blood clearance and mixed renal and hepatobiliary elimination of Mn-TyEDTA. Furthermore, compared to liver-specific and non-specific extracellular contrast agents (Mn-BnO-TyEDTA (BnO-TyEDTA = benzyl tyrosine-derived ethylenediaminetetraacetic acid) and Gd-DTPA (DTPA = diethylene triamine penta-acetic acid)), MRI on a monosodium urate (MSU) crystal-induced acute mice model of arthritis showed that inflamed tissues could be selectively enhanced by Mn-TyEDTA, suggesting that this peroxidase-activatable Mn(II) MRI probe could potentially be used for noninvasive detection of MPO activity in vivo.

Current Imaging Diagnosis of Hepatocellular Carcinoma.

Simple SummaryThe role of imaging in the management of hepatocellular carcinoma (HCC) has significantly evolved and expanded beyond the plain radiological confirmation of the tumor based on the typical appearance in a multiphase contrast-enhanced CT or MRI examination. The introduction of hepatobiliary contrast agents has enabled the diagnosis of hepatocarcinogenesis at earlier stages, while the application of ultrasound contrast agents has drastically upgraded the role of ultrasound in the diagnostic algorithms. Newer quantitative techniques assessing blood perfusion on CT and MRI not only allow earlier diagnosis and confident differentiation from other lesions, but they also provide biomarkers for the evaluation of treatment response. As distinct HCC subtypes are identified, their correlation with specific imaging features holds great promise for estimating tumor aggressiveness and prognosis. This review presents the current role of imaging and underlines its critical role in the successful management of patients with HCC.Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer related death worldwide. Radiology has traditionally played a central role in HCC management, ranging from screening of high-risk patients to non-invasive diagnosis, as well as the evaluation of treatment response and post-treatment follow-up. From liver ultrasonography with or without contrast to dynamic multiple phased CT and dynamic MRI with diffusion protocols, great progress has been achieved in the last decade. Throughout the last few years, pathological, biological, genetic, and immune-chemical analyses have revealed several tumoral subtypes with diverse biological behavior, highlighting the need for the re-evaluation of established radiological methods. Considering these changes, novel methods that provide functional and quantitative parameters in addition to morphological information are increasingly incorporated into modern diagnostic protocols for HCC. In this way, differential diagnosis became even more challenging throughout the last few years. Use of liver specific contrast agents, as well as CT/MRI perfusion techniques, seem to not only allow earlier detection and more accurate characterization of HCC lesions, but also make it possible to predict response to treatment and survival. Nevertheless, several limitations and technical considerations still exist. This review will describe and discuss all these imaging modalities and their advances in the imaging of HCC lesions in cirrhotic and non-cirrhotic livers. Sensitivity and specificity rates, method limitations, and technical considerations will be discussed.

Hepatobiliary phases in magnetic resonance imaging using liver-specific contrast for focal lesions in clinical practice.

BACKGROUNDChallenging 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). AIMTo demonstrate the value of the hepatobiliary phases using gadoxetic acid in MRI for the characterization of focal liver lesions (FLL) in clinical practice.METHODSOverall, 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. RESULTSThe 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. CONCLUSIONThe 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.

Is Gadoxetic Acid Disodium (Gd-EOB-DTPA)-Enhanced Magnetic Resonance Imaging an Accurate Diagnostic Method for Hepatocellular Carcinoma? A Systematic Review with Meta-Analysis.

Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid (Gd- EOB-DTPA) has become a widely used liver-specific contrast agent worldwide, but its value and limitations as a diagnostic technique with Hepatocellular Carcinoma (HCC), have not been assessed. A review of the latest evidence available on the diagnostic value of Gd-EOB-DTPA- enhanced MRI for the evaluation of HCC is reported. A systematic, comprehensive literature search was conducted with PubMed, Scopus, EMBASE, the Web of Science, the Cochrane Library, CNKI, vip, wanfangdata and CBM from inception to June 31, 2020. The QUADAS-2 tool was used to evaluate the quality of the included studies. Pooled Sensitivity (SEN), Pooled Specificity (SPE), pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), pooled diagnostic odds ratio (dOR) and summary receiver operating characteristic (SROC) curves were calculated to assess the diagnostic value of the individual diagnostic tests. A total of 47 articles were included, involving a total of 6362 nodules in 37 studies based on per-lesion studies. There were 13 per-patient studies, including a total of 1816 patients. The results of the meta-analysis showed that the per-lesion studies pooled weighted values were SEN 0.90 [95% confidence interval (CI): 0.87-0.92], SPE 0.92 (95% CI: 0.90-0.94), PLR 11.6 (95% CI: 8.8-15.2), NLR 0.11 (95% CI: 0.09-0.14) and dOR 107.0 (95% CI: 74.0-155.0). The AUC of the SROC curve was 0.96. The per-patient studies pooled weighted values were SEN 0.84 [95% confidence interval (CI): 0.78-0.89], SPE 0.92 (95% CI: 0.88-0.94), PLR 10.4 (95% CI: 7.4-14.6), NLR 0.17 (95% CI: 0.12-0.24) and dOR 61.0 (95% CI: 42.0-87.0). The AUC of the SROC curve was 0.95 and subgroup analyses were performed. The diagnostic value of Gd-EOB-DTPA for HCC was quantitatively evaluated in a per-lesion study and a per-patient study using a systematic review of the literature. A positive conclusion was drawn: Gd-EOB-DTPA-enhanced imaging is a valuable diagnostic technique for HCC. The size of the nodules and the selection of the imaging diagnostic criteria may affect the diagnostic sensitivity.

PET/CT and PET/MRI in neuroendocrine neoplasms.

Advanced molecular imaging has come to play an integral role in the management of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Somatostatin receptor (SSTR) PET has now emerged as the reference standard for the evaluation of NENs and is particularly critical in the context of peptide receptor radionuclide therapy (PRRT) eligibility. SSTR PET/MRI with liver-specific contrast agent has a strong potential for one-stop-shop multiparametric evaluation of GEP-NENs. 18F-FDG is a complementary radiotracer to SSTR, especially in the context of high-grade neuroendocrine neoplasms. Knowledge gaps in quantitative evaluation of molecular imaging studies and their role in assessment of response to PRRT and combination therapies are active research areas. Novel radiotracers have the potential to overcome existing limitations in the molecular imaging of GEP-NENs. The purpose of this article is to provide an overview of the current trends, pitfalls, and recent advancements of molecular imaging for GEP-NENs.