Nina Bastati

Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions

Screening of the liver for hepatic lesion detection and characterization is usually performed with either ultrasound or CT. However, both techniques are suboptimal for liver lesion characterization and magnetic resonance (MR) imaging has emerged as the preferred radiological investigation. In addition to unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate tissue-specific physiological information, thereby facilitating liver lesion characterization. Currently, the classes of contrast agents available for MR imaging of the liver include non-tissue-specific extracellular gadolinium chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this review, we describe the MR features of the more common focal hepatic lesions, as well as appropriate imaging protocols. A special emphasis is placed on the clinical use of non-specific and liver-specific contrast agents for differentiation of focal liver lesions. This may aid in the accurate diagnostic workup of patients in order to avoid invasive procedures, such as biopsy, for lesion characterization. A diagnostic strategy that considers the clinical situation is also presented.

Liver Fibrosis: Histopathologic and Biochemical Influences on Diagnostic Efficacy of Hepatobiliary Contrast-enhanced MR Imaging in Staging

PURPOSE To evaluate the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the staging of liver fibrosis in patients with diffuse chronic liver diseases (CLDs) and to investigate the factors that may influence the results. MATERIALS AND METHODS With the approval of the Hospital Ethics Committee and waiver of the informed consent requirement, data in 102 patients with histologically proven liver fibrosis (classified according to the METAVIR system) of various underlying causes were retrospectively analyzed. Patients underwent 3.0-T MR imaging with gadoxetic acid. The signal intensity of the liver was defined by using region of interest measurements before contrast material injection and in the hepatobiliary phase (20 minutes after contrast material administration), and relative enhancement was calculated. Univariate and multivariate regression analyses were applied to identify variables associated with relative enhancement measurements, and the performance of relative enhancement measurements in the staging of liver fibrosis was assessed by using area under the receiver operating characteristic curve (AUC) analysis. RESULTS At analysis of the relationship between enhancement measurements and histologic parameters, the relative enhancement values correlated strongly with liver fibrosis stage (r = -0.65, P < .0001) and moderately with necroinflammatory activity grades (r = -0.41, P = .002) and the presence of iron load (r = -0.21, P = .05). In multivariate analysis, only liver fibrosis stage independently influenced relative enhancement values (P < .001). The measurements performed well in the staging of liver fibrosis, with an AUC of 0.81 for stages of F1 or greater, 0.82 for stages of F2 or greater, 0.85 for stages of F3 or greater, and 0.83 for stage F4. Increased aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels were independent predictors of false-negative results. CONCLUSION The presence of hepatic fibrosis can be assessed with good discrimination by using gadoxetic acid-enhanced MR imaging, but assessment can be confounded in the setting of abnormal aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels.

Noninvasive Differentiation of Simple Steatosis and Steatohepatitis by Using Gadoxetic Acid–enhanced MR Imaging in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study

PURPOSE To determine whether gadoxetic acid-enhanced magnetic resonance (MR) imaging can be used to distinguish between simple steatosis and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD), defined according to the steatosis activity and fibrosis (SAF) scoring system, which is based on the semiquantitative scoring of steatosis activity and liver fibrosis. MATERIALS AND METHODS The local institutional review committee approved this study and waived written informed consent. This was a retrospective study of gadoxetic acid-enhanced 3-T MR imaging performed in 81 patients with NAFLD (45 men [56%]; mean age, 56 years; range, 25-78 years). The MR images were analyzed by using the relative enhancement (the ratio of signal intensities of the liver parenchyma before and 20 minutes after intravenous administration of gadoxetic acid). Univariate and multiple regression analyses were applied to identify variables associated with relative enhancement measurements. The ability of relative enhancement to allow differentiation between simple steatosis and NASH was assessed by using area under the receiver operating characteristic (ROC) curve analysis. RESULTS Relative enhancement negatively correlated with the degree of lobular inflammation (r = -0.59, P < .0001), ballooning (r = -0.44, P < .0001), and fibrosis (r = -0.59, P ≤ .0001), but not with steatosis (r = -0.16, P = .15). Patients with NASH had a significantly lower relative liver enhancement (0.82 ± 0.22) than those with simple steatosis (1.39 ± 0.52) (P < .001). Relative enhancement measurements performed well in the differentiation between simple steatosis and NASH, with an area under the ROC curve of 0.85 (95% confidence interval: 0.75, 0.91) (cutoff = 1.24, sensitivity = 97%, specificity = 63%). CONCLUSION Gadoxetic acid relative enhancement was significantly lower in patients with NASH than in patients with simple steatosis, but further prospective studies are warranted.

Morphologic and Molecular Features of Hepatocellular Adenoma with Gadoxetic Acid–enhanced MR Imaging

PURPOSE To evaluate the diagnostic performance of imaging features of gadoxetic acid-enhanced magnetic resonance (MR) imaging to differentiate among hepatocellular adenoma (HCA) subtypes by using the histopathologic results of the new immunophenotype and genotype classification and to correlate the enhancement pattern on the hepatobiliary phase (HBP) with the degrees of expression of organic anion transporting polypeptide (OATP1B1/3), multidrug resistance-associated protein 2 (MRP) (MRP2), and MRP 3 (MRP3) transporters. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement for informed consent waived. MR imaging findings of 29 patients with 43 HCAs were assessed by two radiologists independently then compared with the histopathologic analysis as the standard of reference. Receiver operating characteristic curves and Spearman rank correlation coefficient were used to test the diagnostic performance of gadoxetic acid-enhanced MR imaging features, which included the retention or washout at HBP and degree of transporter expression. Interreader agreement was assessed by using the κ statistic with 95% confidence interval. RESULTS The area under the curve for the diagnosis of inflammatory HCA was 0.79 (95% confidence interval: 0.64, 0.90); for the steatotic type, it was 0.90 (95% confidence interval: 0.77, 0.97); and for the β-catenin type, it was 0.87 (95% confidence interval: 0.74, 0.95). There were no imaging features that showed a significant statistical correlation for the diagnosis of unclassified HCAs. On immunohistochemical staining, OATP1B1/3 expression was the main determinant for the retention, whereas MRP3 was the key determinant for washout of gadoxetic acid at HBP (P < .001). MRP2 appeared to have no role. CONCLUSION Gadoxetic acid-enhanced MR imaging features may suggest the subtype of HCA. The degree of OATP1B1/3 and MRP3 expression correlated statistically with gadoxetic acid retention and washout, respectively, in the HBP.

Texture-based classification of different gastric tumors at contrast-enhanced CT

PURPOSE To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. MATERIALS AND METHODS The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n=4, G1, n=4; AC-G2, n=7; AC-G3, n=16]; GIST, n=15; and lymphoma, n=5, and the venous phase scans of 48 patients with AC-G1, n=3; AC-G2, n=6; AC-G3, n=14; GIST, n=17; lymphoma, n=8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. RESULTS On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. CONCLUSION Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two histological subtypes.

Magnetic resonance imaging of liver malignancies.

The histological structure of the liver is complex, consisting of hepatocytes, biliary epithelium, and mesenchymal cells. From this large variety of cells, a broad spectrum of benign and malignant liver lesions in originate. An accurate diagnosis of these lesions is mandatory for choosing an appropriate therapeutic approach. With the recent developments in hardware and software, magnetic resonance imaging (MRI) has emerged as the method of choice in the diagnostic workup of focal liver lesions, in particular in the pretherapeutic stage. The introduction of high-field MRI at 3.0T in the routine workup and the selective use of liver-specific contrast agents, including hepatobiliary and reticuloendothelial agents, have also strengthened the role of MRI in liver imaging. In this overview article, we will review the recent developments in 3.0-T MRI and MRI contrast agents in the diagnostic workup of the most common malignant liver tumors.

MR Imaging of Benign Focal Liver Lesions

MRI has become the most important imaging modality for detecting and characterizing focal liver lesions. The introduction of high-field-strengths, such as 3 Tesla MR imaging, in combination with the parallel imaging technique, has led to significant improvements in spatial and temporal resolution and has established this technique as a valuable asset in daily clinical practice. New techniques, such as diffusion-weighted imaging, may improve MR imaging sensitivity and specificity in the diagnostic workup of focal liver lesions. The tailored administration of various nonspecific and liver-specific contrast agents enables clinicians to increase the detection rate and improve the characterization of the different focal liver lesions. This article describes the usefulness of these imaging techniques in detecting and characterizing the most common benign focal liver lesions.

P4 radiology of hepatobiliary diseases with gadoxetic acid-enhanced MRI as a biomarker

A recent paradigm shift in radiology has focused on the globalization of so-called P4 radiology. P4 radiology represents delivery of imaging results that are predictive, personalized, pre-emptive and participatory. The combination of the P4 approach and biomarkers is particularly pertinent to MRI, especially with technological advances such as diffusion-weighted imaging. The development of new liver-specific MRI contrast media, particularly gadoxetic acid, demonstrate specific pharmacokinetic properties, which provide combined morphologic and functional information in the same setting. The evaluation of hepatobiliary pathology beyond morphology gives rise to the possibilty of using gadoxetic acid-enhanced MRI as an imaging biomarker of hepatobiliary diseases. The integration of functional imaging with an understanding of complex disease mechanisms forms the basis for P4 radiology, which may ultimately lead to individualized, cost-effective, targeted therapy for patients. This will enable radiologists to determine the prognosis of the disease and estimate early response to treatment, with the participation of all the required medical disciplines.

Imaging of the Stomach and Esophagus Using CT and PET/CT Techniques

Multidetector computed tomography (MDCT) is the most frequently employed modality in the diagnostic evaluation of oncologic diseases of the abdomen and pelvis. Although upper-GI series have been used to evaluate the spectrum of infectious, inflammatory, and neoplastic esophageal and gastric diseases, fluoroscopic studies are limited in their ability to provide staging information about the status of gastric and esophageal tumors, including the presence of local and regional spread of tumor, as well the presence of distant metastases. By virtue of its ability to provide a global perspective of the gut wall, adjacent fat, and lymph nodes, as well as local and distal organs, CT has virtually replaced fluoroscopic techniques in the oncology patient, except for the evaluation of postoperative complications, swallowing, and esophageal motility disorders.

The Efficacy of MRI in the diagnostic workup of cystic fibrosis-associated liver disease: A clinical observational cohort study

PurposeTo identify independent imaging features and establish a diagnostic algorithm for diagnosis of cystic fibrosis (CF)-associated liver disease (CFLD) in CF patients compared to controls using gadoxetic acid-enhanced MRI.MethodsA total of 90 adult patients were enrolled: 50 with CF, 40 controls. The CF group was composed of two subgroups: a retrospective test subgroup (n = 33) and a prospective validation subgroup (n = 17). Controls (patients with normal liver enzymes and only benign focal liver lesions) were divided accordingly (27:13). MRI variables, including quantitative and qualitative parameters, were used to distinguish CFLD from controls using clinical symptoms, laboratory tests and Debray criteria. Disease severity was classified according to Child-Pugh and Albumin-Bilirubin (ALBI) scores. Fifteen qualitative single-lesion CF descriptors were defined. Two readers independently evaluated the images. Univariate statistical analysis was performed to obtain significant imaging features that differentiate CF patients from controls. Through multivariate analysis using chi-squared automatic interaction detector (CHAID) methodology the most important descriptors were identified. Diagnostic performance was assessed by receiver-operating characteristic (ROC) analysis.ResultsThree independent imaging descriptors distinguished CFLD from controls: (1) presence of altered gallbladder morphology; (2) periportal tracking; and (3) periportal fat deposition. Prospective validation of the classification algorithm demonstrated a sensitivity of 94.1% and specificity of 84.6% for discriminating CFLD from controls. Disease severity was well associated with the imaging features.ConclusionsA short unenhanced MRI protocol can identify the three cardinal imaging features of CFLD. The hepatobiliary phase of gadoxetic acid-enhanced MRI can define CFLD progression.Key Points• Using a multivariate classification analysis, we identified three independent imaging features, altered gallbladder morphology (GBAM), periportal tracking (PPT) and periportal fat deposition (PPFD), that could diagnose CFLD with high sensitivity, 94.1 % (95% CI: 71.3–99.9) and moderate specificity, 84.6 % (95% CI: 54.6–98.1).• Based upon the results of this study, gadoxetic acid-enhanced MRI with DWI is able to diagnose early-stage CFLD, as well as its progression.