Comparative Diagnostic Performance of Multiparametric Ultrasound Versus Contrast-Enhanced Computed Tomography the Differential Diagnosis of Focal Liver Lesions in Colorectal Cancer

The implications of endoscopic ultrasound (EUS) have expanded considerably in recent years to cover more fields in invasive gastroenterology practice, as both an investigative and therapeutic modality. The utility of EUS in the diagnosis and management of focal liver lesions has gained a special attractiveness recently. The EUS probe proximity to the liver and its excellent spatial resolution enables real-time images coupled with several enhancement techniques, such as contrast-enhanced (CE) EUS. Aside from its notable capability to execute targeted biopsies and therapeutic interventions, EUS has developed into a hopeful therapeutic tool for the management of solid liver lesions. Herein, we provide a comprehensive state-of-the-art review on the efficacy and safety of EUS in the diagnosis and management of focal solid liver lesions. Medline/PubMed and Embase database searches were conducted by two separate authors (T.K. and W.S.), all relevant studies were assessed, and relevant data was extracted and fully reported. EUS-guided diagnosis of focal liver lesions by sonographic morphologic appearance and cytological and histopathological finding of biopsies obtained via fine needle aspiration/biopsy have been shown to significantly improve the diagnosis of solid liver lesions compared with traditional imaging tools. Similarly, EUS-guided treatment has been shown to consistently have excellent technical success, high efficacy, and minor adverse events. The evolving valuable evidences of EUS utility might satisfy the unmet need of optimizing management of focal solid liver lesions.

To investigate the clinical value of acoustic radiation force impulse (ARFI) elastography in the differential diagnosis of focal liver lesions. ARFI elastography was performed for 169 lesions from 163 patients with focal liver lesions and 15 healthy volunteers, and the virtual touch tissue imaging (VTI) findings and measured value of shear wave velocity (SWV) of liver lesions were obtained and compared between groups. The t-test was applied for comparison of means between two groups; the one-way analysis of variance was applied for comparison of means between multiple groups, and the Student-Newman-Keuls test was applied for further comparison between any two groups. Benign focal liver lesions were stiffer or softer than or had the same stiffness as the surrounding liver parenchyma. These lesions had a uniform texture, and the ratio between their diameters on elastographic images and two-dimensional images was close to 1. The typical VTI finding of hemangioma lesions was"honeycomb"pattern. Most malignant focal liver lesions were stiffer than the surrounding liver parenchyma, and the ratio between their diameters on elastographic images and two-dimensional images was greater than 1. The typical VTI finding of metastatic lesions was"bull's eye"sign. With a measured SWV of 2.08 m/s as the diagnostic threshold for malignant liver lesions, its sensitivity, specificity, and accuracy were 90.3%, 76.9%, and 84.2%, respectively. Poorly differentiated hepatocellular carcinoma (HCC) showed a significant increase in stiffness compared with moderately differentiated HCC (t = 5.319, P = 0.025) and well-differentiated HCC (t = 6.372, P = 0.011). ARFI elastography can reflect changes in the stiffness of focal liver lesions accurately, and is useful for the differential diagnosis of benign and malignant focal liver lesions.

Notably, the number of incidentally detected focal liver lesions (FLLs) has increased dramatically in recent years due to the increased use of radiological imaging. The diagnosis of FLLs can be made through a well-documented medical history, physical examination, laboratory tests, and appropriate imaging methods. Although benign FLLs are more common than malignant ones in adults, even in patients with primary malignancy, accurate diagnosis of incidental FLLs is of utmost clinical significance. In clinical practice, FLLs are frequently evaluated non-invasively using ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Although US is a cost-effective and widely used imaging method, its diagnostic specificity and sensitivity for FLL characterization are limited. FLLs are primarily characterized by obtaining enhancement patterns through dynamic contrast-enhanced CT and MRI. MRI is a problem-solving method with high specificity and sensitivity, commonly used for the evaluation of FLLs that cannot be characterized by US or CT. Recent technical advancements in MRI, along with the use of hepatobiliary-specific MRI contrast agents, have significantly improved the success of FLL characterization and reduced unnecessary biopsies. The American College of Radiology (ACR) appropriateness criteria are evidence-based recommendations intended to assist clinicians in selecting the optimal imaging or treatment option for their patients. ACR Appropriateness Criteria Liver Lesion-Initial Characterization guideline provides recommendations for the imaging methods that should be used for the characterization of incidentally detected FLLs in various clinical scenarios. The American College of Gastroenterology (ACG) Clinical Guideline offers evidence-based recommendations for both the diagnosis and management of FLL. American Association for the Study of Liver Diseases (AASLD) Practice Guidance provides an approach to the diagnosis and management of patients with hepatocellular carcinoma. In this article, FLLs are reviewed with a comprehensive analysis of ACR Appropriateness Criteria, ACG Clinical Guideline, AASLD Practice Guidance, and current medical literature from peer-reviewed journals. The article includes a discussion of imaging methods used for the assessment of FLL, current recommended imaging techniques, innovations in liver imaging, contrast agents, imaging features of common nonmetastatic benign and malignant FLL, as well as current management recommendations.

A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT.

Rationale: The differential diagnosis of focal liver lesions remains challenging, particularly in situations where the use of contrast agents in magnetic resonance imaging (MRI) is contraindicated (e. g., due to renal failure or allergy) or when the findings on T2-weighted images (T2WI) lack any pathognomonic signs. In these scenarios, an additional diagnostic tool is required to support decision-making, and a clinical-radiomic model capable of accurately classifying focal lesions based on T2WI data with accuracy and precision could be relevant. Aim: To develop and perform internal validation of a clinical-radiomic model for the differential diagnosis of focal liver lesions based on T2WI. Methods: This was a retrospective cross-sectional single-center study with an open anonymized WORC-Liver dataset, containing T2WI abdominal MRI images of patients with focal liver lesions (the original data collection performed at Erasmus Medical Center (Rotterdam, the Netherlands) between 2002 and 2018 using 1.5T Siemens, Philips, and General Electric scanners). Image processing included normalization (SimpleITK, Z-score) and interpolation to isotropic 1 × 1 × 1 mm³ voxels. Radiomic feature extraction was performed using intensity histograms and gray-level matrices (PyRadiomics). The characteristics were classified using the XGBoost algorithm with an 80:20 train-validation split. Results: From the initial dataset of 186 cases, 146 patients (72 with malignant and 74 with benign lesions) were selected for analysis. On the internal validation set (n = 30), the model showed high diagnostic performance: ROC-AUC 96% (95% confidence interval [CI]: 0.89–1.00), sensitivity 87% (95% CI: 77–97), specificity 93% (95% CI: 85–100). The analysis of variable importance revealed the largest contributions from the following ones: patient age (SHAP +0.88), manufacturer: GE (SHAP +0.35), patient sex (SHAP +0.29), and original_gldm_DependenceNonUniformity (SHAP +0.17). Conclusion: We were able to develop a high-accuracy clinical-radiomic model for the non-invasive differential diagnosis of focal liver lesions using native T2WI. The results demonstrate the model's potential for clinical application, particularly when the contrast administration is contraindicated. Its implementation would require further validation in larger and more diverse datasets.

Ultrasonography (US) has the overwhelming advantages of not entailing radiation exposure and being a noninvasive, real-time, convenient, easy-to-perform, and relatively inexpensive imaging modality. It is used as the first-line imaging modality for screening, detection, and diagnosis of focal liver lesions (FLLs) [small hepatocellular carcinomas (HCCs), in particular]. However, with the increasing demand for accurate and early diagnosis of small HCCs, newer radiologic methods need to be explored to overcome certain limitations of US. For example, the imaging is easily negatively affected by the presence of gas, rib cage, and subcutaneous fat, and is insensitive for capturing the subtle but vital information on the blood flow. It was in response to this need that new promising technologies such as contrast-enhanced ultrasound and fusion imaging were introduced for the detection of liver lesions. This paper presents an overview of the epidemiology and mechanisms of the development of HCCs, with an emphasis on the application of US in the diagnosis and treatment of FLLs. The aim of this article is to provide the state-of-the-art developments in the imaging diagnosis of FLLs and evaluation of ablation treatment of early HCCs. By keeping abreast of these recent advances, we hope that doctors and researchers working in the field of diagnosis/treatment of liver diseases will be able to discriminate benign FLLs such as regenerative nodules and focal nodular hyperplasia from HCCs, so as to avoid unnecessary repeated tumor biopsies and overtreatment. In particular, we expect that small HCCs or precancerous nodules (such as dysplastic nodules) can be accurately diagnosed and appropriately treated even at an early stage.

Differential diagnosis of CT focal liver lesions using texture features, feature selection and ensemble driven classifiers

Objectives: To determine the diagnostic accuracy of triphasic CT in the diagnosis of focal liver lesions as benign or malignant by using histopathology as the gold standard. Methods: This descriptive cross-sectional study was carried out at the diagnostic radiology department of the Pakistan Institute of Medical Sciences (P.I.M.S.) in Islamabad.110 individuals with localized liver lesions between the ages of 15 and 65 years and both genders were included. All of the study subjects were then undergoing triphasic CT scan of the liver. The CT findings were recorded as benign or malignant and correlated with histopathology findings. Data collection was done by using the self-structured proforma. Results: Patient’s mean age was 43.92 ± 12.87 years. Out of all, males were 68 (61.82%) and females were 42 (38.18%), with a female-to-male ratio of 1:1.6. Malignant lesions were 73 (66.36%) and 37 (33.54%) patients had benign lesions as per Triphasic CT diagnosis. Furthermore, in these 73 malignant cases, 67 cases were observed with malignant lesions and 6 cases had benign lesions on histopathology, while among the 37 CT cases of benign lesions, 8 cases had malignant lesions as per the histopathological diagnosis. Although triphasic CT showed 89.33% sensitivity and 82.86% specificity in the diagnosis of focal liver lesions by using histopathology as the gold standard. Conclusion: Triphasic CT was observed to be a non-invasive, accurate, and highly sensitive imaging technique in the diagnosis of focal liver lesions, whether (benign or malignant). Therefore, it can be used frequently to lower the number of pure diagnostic biopsies. Keywords: Malignant hepatic lesions, non-invasive, imaging modality, sensitivity

Liver specific phase of perflubutane microbubbles contrast-enhanced ultrasound for potential use in the diagnosis of focal liver lesions

Objective To investigate the initial clinical value of shear wave elastography (SWE) combined with shear wave dispersion (SWD) in preoperatively differentiating diagnosis of focal liver lesions (FLLs). Methods Eighty-three patients diagnosed as FLLs were prospectively enrolled from January to April 2018 in Zhongshan Hospital of Fudan University. Measurements of SWD and SWE both inner FLLs and surrounding liver parenchyma 2 cm away from the board lines of lesions were performed. ROIs were placed within the lesions and surrounding parenchyma 2 cm away from the lesions. In each ROI, measurements were performed 13 times. Histopathological results after operation were regarded as gold standard, and the values of viscoelasticity in differentiating diagnosis of FLLs were analyzed. Results The final histopathological results showed that of all 83 cases, 20 cases were diagnosed as benign lesions (5 cases of focal nodular hyperplasia, 15 cases of hemangioma), and 63 cases as malignant lesions (12 cases of liver metastases, 51 cases of hepatocellular carcinoma). The SWE of benign lesions and malignant lesions were (9.94±8.22)kPa, and (13.68±7.80)kPa(P<0.05). The SWD of benign lesions and malignant lesions were (13.47±2.76)(m/s)/kHz, and (15.00±3.82)(m/s)/kHz(P<0.05). The SWE ratio and SWD ratio of benign lesions to surrounding liver parenchyma were higher than those of malignant lesions(all P<0.05). The SWE ratio of benign and malignant lesions were 2.60±2.65, and 1.40±1.40, respectively (P<0.05). The SWD ratio of benign and malignant lesions were 0.92±0.44, and 0.80±0.51, respectively(P<0.05). Conclusions With the advantages of effectiveness, convenience, non-invasiveness and repeatability, combined measurement of SWE and SWD has a potential value in differentiating diagnosis of liver lesions. Key words: Shear wave elastography; Shear wave dispersion; Viscoelasticy; Liver neoplasms; Differential diagnosis

Evaluation of tissue harmonic imaging for the diagnosis of focal liver lesions

Aim: The aim was to evaluate the diagnostic value of contrast-enhanced ultrasound in the differential diagnosis of focal liver lesions, in a blinded experiment. In clinical routine the examiner can generally be influenced by the patient’s history. Method: 62 patients with focal liver lesions, which could not be clearly differentiated and diagnosed by conventional ultrasound, were examined with contrast-enhanced (BR1, SonoVue^®, Bracco) ultrasound and included in a blinded prospective and randomized study. The examinations performed on a Sequoia 512 (Acuson) in a coherent contrast imaging method were recorded by an S-VHS recorder and afterwards analyzed by an examiner who did not know the patient’s history. The basis of the diagnosis was the dynamic appearance and enhancement of the ultrasound contrast enhancer in different phases of liver perfusion. The conformation of the diagnoses was made by corresponding reference methods, as computer tomography, magnetic resonance imaging, biopsy and clinical follow-up. Results: The following diagnoses were confirmed by reference methods: 18 patients with metastases, 4 hepatocellular carcinomas, 19 haemangiomas, 6 focal nodular hyperplasias, 13 patients with focal fatty infiltration and 2 patients with focal fatty sparing. 59 out of 62 patients with one or more liver lesions were correctly diagnosed by contrast-enhanced ultrasound. Conclusion: Second-generation ultrasound contrast enhancers improve the differential diagnosis of benign and malignant liver lesions considerably, especially in a blinded study.

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.

Despite the great technical achievements in the field of tomographic examinations (CT, MRI), the problem of differentiation of focal liver lesions cannot always be solved only in a non-invasive way. At the same time, MRI with a hepatospecific agent, gadoxetic acid, can solve many problems, primarily related to the diagnosis of liver metastases and monitoring of nodules in cirrhotic liver. The aim. To show the advantages of MRI with hepatobiliary MRI contrast agents as the final phase of non-invasive diagnosis of focal liver lesions. Material and methods . Abstracts of 183 scientific articles (2010–2019) were selected in the PubMed information and analytical system for the keywords "focal liver lesion" and "gadoxetic acid". Articles about special aspects of MRI examination or general information were excluded. 29 full-text articles were selected for analysis. Results . The analysis data are grouped in three categories as "diagnosis of liver metastases", "diagnosis of HCC against the background of normal hepatic parenchyma", "MRI diagnosis of HCC against the background of cirrhosis". Conclusion. The main achievement of MRI diagnostics with gadoxetic acid is the differentiation of small focal liver lesions, including metastases, regenerative nodes, dysplastic nodes, and highly differentiated HCC. This allows you to increasingly avoid invasive methods in the diagnosis of focal liver lesions. Integrated MRI technologies (MRI-DVI and MRI with gadoxetic acid) are currently the most informative, safe and in demand. In MRI with hepatobiliary contrast agents, the intensity of the HCC signal in the hepatospecific phase is considered as an imaging tumor biomarker. Border small liver nodules are usually not hypervascular, they are hypointensive in the hepatospecific phase.

Quantitative analysis of gadoxetic acid-enhanced MRI for the differential diagnosis of focal liver lesions: Comparison between estimated intralesional gadoxetic acid retention by T1 mapping and conventional processing methods