Elastography for Pediatric Chronic Liver Disease: A Review and Expert Opinion.

In adults with chronic liver diseases, ultrasound and magnetic resonance shear wave elastography (SWE) can replace liver biopsy in several clinical scenarios. Several guidelines on the use of ultrasound SWE for the adult population have been published. However, the number of publications in the pediatric population is limited, and available guidelines on SWE do not specifically address pediatric chronic liver diseases. In this article, we review the literature on the use of SWE for pediatric chronic liver diseases and provide expert opinion on how to use SWE, both ultrasound and magnetic resonance techniques, in the pediatric population.

Review of Liver Elastography Guidelines.

Nowadays, shear wave elastographic techniques have brought a substantial reduction of liver biopsies performed to stage liver fibrosis in patients with chronic hepatitis. The availability of accurate noninvasive methods for the assessment of liver fibrosis was an important breakthrough and prompted ultrasound federations of societies as well as clinical and radiologic societies to issue international guidelines or consensus statements on the clinical applications of shear wave elastographic techniques. This article reviews the guidelines that have been published as of today.

[Functional MR imaging of the liver]. / Funktionelle MR-Tomographie der Leber.

The diagnostics of diffuse liver disease traditionally rely on liver biopsies and histopathological analysis of tissue specimens. However, a liver biopsy is invasive and carries some non-negligible risks, especially for patients with decreased liver function and those requiring repeated follow-up examinations. Over the last decades, magnetic resonance imaging (MRI) has developed into a valuable tool for the non-invasive characterization of focal liver lesions and diseases of the bile ducts. Recently, several MRI methods have been developed and clinically evaluated that also allow the diagnostics and staging of diffuse liver diseases, e.g. non-alcoholic fatty liver disease, hepatitis, hepatic fibrosis, liver cirrhosis, hemochromatosis and hemosiderosis. The sequelae of diffuse liver diseases, such as a decreased liver functional reserve or portal hypertension, can also be detected and quantified by modern MRI methods. This article provides the reader with the basic principles of functional MRI of the liver and discusses the importance in a clinical context.

Effect of temporal resolution on 4D flow MRI in the portal circulation.

PURPOSE: To demonstrate the use of temporal averaging with radial 4D flow magnetic resonance imaging (MRI) to reduce scan time for quantification and visualization of flow in the portal circulation. This study compared phase-contrast MR angiography, 3D flow visualization, and flow quantification of portal venous hemodynamics of time-averaged vs. time-resolved reconstructions. MATERIALS AND METHODS: Time-resolved 3D radial ("4D") phase contrast data were acquired from 44 subjects (15 volunteers, 29 cirrhosis patients) at 3T. Images were reconstructed as a fully sampled time-resolved reconstruction and multiple time-averaged reconstructions using a variable number of acquired projections to simulate different scan times. Images from each reconstruction were evaluated to compare the quality of anatomical and hemodynamic visualization. RESULTS: Time-averaged reconstructions outperformed time-resolved reconstructions for flow quantification (3.9 ± 3.1% error vs. 5.2 ± 4.4% error), average streamline length (47 ± 7 mm vs. 34 ± 15 mm), and visualization quality (average grading = 3.7 ± 0.5 vs. 2.2 ± 0.9). In addition, excellent visualization quality was achieved using fewer acquired projections. CONCLUSION: Reductions in scan time can be achieved through time-averaging while still providing excellent visualization and quantification in the portal circulation. Scan time reduction of up to 70%-80% was possible for high-quality assessment, translating into a reduction in scan time from 10-12 minutes to ∼3-4 minutes.

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PURPOSE: Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. MATERIALS AND METHODS: Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. RESULTS: AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. CONCLUSION: AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC.

Liver Magnetic Resonance Elastography: Focus on Methodology, Technique, and Feasibility.

Magnetic resonance elastography (MRE) is an imaging technique that combines low-frequency mechanical vibrations with magnetic resonance imaging to create visual maps and quantify liver parenchyma stiffness. As in recent years, diffuse liver diseases have become highly prevalent worldwide and could lead to a chronic condition with different stages of fibrosis. There is a strong necessity for a non-invasive, highly accurate, and standardised quantitative assessment to evaluate and manage patients with different stages of fibrosis from diagnosis to follow-up, as the actual reference standard for the diagnosis and staging of liver fibrosis is biopsy, an invasive method with possible peri-procedural complications and sampling errors. MRE could quantitatively evaluate liver stiffness, as it is a rapid and repeatable method with high specificity and sensitivity. MRE is based on the propagation of mechanical shear waves through the liver tissue that are directly proportional to the organ's stiffness, expressed in kilopascals (kPa). To obtain a valid assessment of the real hepatic stiffness values, it is mandatory to obtain a high-quality examination. To understand the pearls and pitfalls of MRE, in this review, we describe our experience after one year of performing MRE from indications and patient preparation to acquisition, quality control, and image analysis.

Heterogeneous Pathological Changes in Liver Lobes During Liver Disease: A Perspective Review.

Liver diseases have a global prevalence of 25%, accounting for 4% of all deaths worldwide, and are associated with a 36% increased risk of fatal and nonfatal cardiovascular events. Metabolic dysfunction-associated steatotic liver disease constitutes the liver expression of metabolic syndrome and represents the primary type of liver disease. Microscopical analysis of biopsies, which allows the evaluation of a small portion of tissue with inferences made to the entire organ, is considered the gold standard for determining the presence of liver diseases. However, potential sampling errors in liver biopsies are conceivable because the obtained tissue represents only a tiny fraction of the entire liver mass and may not accurately reflect the true pathological state. Studies have demonstrated the existence of sampling errors in liver biopsies, particularly concerning the severity of inflammation, degree of fibrosis, and the presence of cirrhosis. Also, clinical studies have shown that histopathological abnormalities are better detected in humans when liver samples are collected from both the right and the left lobes. However, a gap exists in clinical investigation to clarify the role of differences between these lobes in improving the diagnostic and prognostic for liver diseases. Building upon the heterogeneous nature of pathological alterations observed in liver lobes, this perspective review provided recommendations to enhance the precision of diagnosis and prognostic accuracy of liver diseases.

Quantitative analysis of tissue area of endoscopic ultrasound-guided liver biopsy specimens using 19-gauge fine-needle biopsy needle in patients with diffuse liver disease: A single-center retrospective study.

BACKGROUND/PURPOSE: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is a novel liver biopsy technique. We aimed to evaluate the efficacy and safety of EUS-LB in comparison with percutaneous liver biopsy (PLB). METHODS: This retrospective study evaluated the safety and efficacy of EUS-LB using a 19-gauge fine needle biopsy (FNB) needle compared with PLB using a spring-loaded 16-gauge needle in patients with diffuse liver disease at our hospital from April 2017 to December 2020. The primary outcomes included the total hepatic tissue surface area and the total number of portal tracts. Secondary outcomes included the success and adverse event rates. RESULTS: Twenty patients each underwent EUS-LB and PLB. There was no statistical difference in the sum of liver tissue surface area (22 mm2 vs 22.6 mm2 , P = .910) and the total number of portal tracts (29 vs 25, P = .916). The success rate was 95% (19/20) for EUS-LB and 100% (20/20) for PLB (P = 1). There were two adverse events in the PLB group but none in the EUS-LB group (P = .487). CONCLUSIONS: Endoscopic ultrasound-guided liver biopsy using FNB has an optimal tissue yield and success rate and is safe compared to PLB. Thus, EUS-LB may be a new alternative to PLB.

[Artificial intelligence technology enables ultrasonography in precision diagnosisand treatment of liver diseases].

Liver disease is one of the major problems affecting human health. Ultrasound plays an important role in diagnosis and treatment of diffuse and focal liver diseases. However, conventional ultrasound evaluation is subjective and provides limited information. Artificial intelligence (AI) technology may supplement the disadvantages of conventional ultrasound and has been widely used in the field of ultrasound in liver diseases. To date, remarkable progress has been achieved for the use of AI technology in the diagnosis, assessment of therapeutic efficacy and prognosis prediction of liver diseases. This paper reviews the research progress of ultrasound image-based AI technology in the diagnosis and treatment of diffuse and focal liver diseases.

The Effect of Diffuse Liver Diseases on the Occurrence of Liver Metastases in Cancer Patients: A Systematic Review and Meta-Analysis.

This systematic review with meta-analysis aimed to assess the effect of diffuse liver diseases (DLD) on the risk of synchronous (S-) or metachronous (M-) liver metastases (LMs) in patients with solid neoplasms. Relevant databases were searched for systematic reviews and cross-sectional or cohort studies published since 1990 comparing the risk of LMs in patients with and without DLD (steatosis, viral hepatitis, cirrhosis, fibrosis) in non-liver solid cancer patients. Outcomes were prevalence of S-LMs, cumulative risk of M-LMs and LM-free survival. Risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale. We report the pooled relative risks (RR) for S-LMs and hazard ratios (HR) for M-LMs. Subgroup analyses included DLD, primary site and continent. Nineteen studies were included (n = 37,591 patients), the majority on colorectal cancer. ROB appraisal results were mixed. Patients with DLD had a lower risk of S-LMs (RR 0.50, 95% CI 0.34-0.76), with a higher effect for cirrhosis and a slightly higher risk of M-LMs (HR 1.11 95% CI, 1.03-1.19), despite a lower risk of M-LMs in patients with vs without viral hepatitis (HR 0.57, 95% CI 0.40-0.82). There may have been a publication bias in favor of studies reporting a lower risk for patients with DLD. DLD are protective against S-LMs and slightly protective against M-LMs for viral hepatitis only.

Sources of Variability in Shear Wave Speed and Dispersion Quantification with Ultrasound Elastography: A Phantom Study.

There is a growing interest in quantifying shear-wave dispersion (SWD) with ultrasound shear-wave elastography (SWE). Recent studies suggest that SWD complements shear-wave speed (SWS) in diffuse liver disease diagnosis. To accurately interpret these metrics in clinical practice, we analyzed the impact of operator-dependent acquisition parameters on SWD and SWS measurements. Considered parameters were the acquisition depth, lateral position and size of the region of interest (ROI), as well as the size of the SWE acquisition box. Measurements were performed using the Canon Aplio i800 system (Canon Medical Systems, Otawara, Tochigi, Japan) and four homogeneous elasticity phantoms with certified stiffness values ranging from 3.7 to 44 kPa. In general, SWD exhibited two to three times greater variability than SWS. The acquisition depth was the main variance-contributing factor for both SWS and SWD, which decayed significantly with depth. The lateral ROI position contributed as much as the acquisition depth to the total variance in SWD. Locations close to the initial shear-wave excitation pulse were more robust to biases because of inaccurate probe-phantom coupling. The size of the ROI and acquisition box did not introduce significant variations. These results suggest that future guidelines on multiparametric elastography should account for the depth- and lateral-dependent variability of measurements.

Diffusion-weighted imaging and texture analysis: current role for diffuse liver disease.

Multiparametric MRI represents the primary imaging modality to assess diffuse liver disease, both in a qualitative and in a quantitative manner. Diffusion-weighted imaging (DWI) is among the imaging techniques that can be used to assess fibrosis due to its unique capability to assess microstructural changes at the tissue level. DWI is based on water mobility patterns and has the potential to become a non-invasive and non-destructive virtual biopsy to assess diffuse liver disease, overcoming sampling bias errors due to its three-dimensional imaging capabilities. Parallel to DWI, another quantitative method called texture analysis may be used to assess early and advanced diffused liver disease through quantifying spatial relationships in a global and local level, applying to any type of digital imaging technique like MRI or CT. Initial results using texture analysis hold great promise. In the current paper, we will review the role of DWI and texture analysis using MR images in assessing diffuse liver disease.

Morphometric changes and imaging findings of diffuse liver disease in relation to intrahepatic hemodynamics.

Diffuse hepatic diseases have a variety of etiologies, with each showing characteristic morphometric changes. These changes are closely related to micro- and macro-level intrahepatic hemodynamics, in addition to the specific underlying pathophysiology. Short-term disorders in intrahepatic hemodynamics caused by each pathophysiological condition are compensated for by the balance of blood perfusion systems using potential trans-sinusoidal, transversal, and transplexal routes of communication (micro-hemodynamics), while long-term alterations to the intrahepatic hemodynamics result in an increase in total hepatic vascular resistance. Blood flow disorders induced by this increased vascular resistance elicit hepatic cellular necrosis and fibrosis. These changes should be uniformly widespread throughout the whole liver. However, morphometric changes do not occur uniformly, with shrinkage or enlargement not occurring homogeneously. Against this background, several macro-intrahepatic hemodynamic effects arise, such as asymmetrical and complicating morphometric structures of the liver, intricate anatomy of portal venous flow and hepatic venous drainage, and zonal differentiation between central and peripheral zones. These hemodynamic factors and pathophysiological changes are related to characteristic morphometric changes in a complicated manner, based on the combination of selective atrophy and compensatory hypertrophy (atrophy-hypertrophy complex). These changes can be clearly depicted on CT and MR imaging.

Dual-energy CT in diffuse liver disease: is there a role?

Dual-energy CT (DECT) can be defined as the use of two different energy levels to identify and quantify material composition. Since its inception, DECT has benefited from remarkable improvements in hardware and clinical applications. DECT enables accurate identification and quantification of multiple materials, including fat, iron, and iodine. As a consequence, multiple studies have investigated the potential role of DECT in the assessment of diffuse liver diseases. While this role is evolving, this article aims to review the most relevant literature on use of DECT for assessment of diffuse liver diseases. Moreover, the basic concepts on DECT techniques, types of image reconstruction, and DECT-dedicated software will be described, focusing on the areas that are most relevant for the evaluation of diffuse liver diseases. Also, we will review the evidence of added value of DECT in detection and assessment of hepatocellular carcinoma which is a known risk in patients with diffuse liver disease.

Ultrasound of Diffuse Liver Disease Including Elastography.

Diffuse liver disease is a substantial world-wide problem. With the combination of conventional ultrasound of the abdomen and elastography-appropriate staging of the patient can be assessed. This information allows for the detection of fibrosis as well as prognosis, surveillance, and prioritization for treatment. With the potential for reversibility with appropriate treatment, accurate assessment for the stage of chronic liver disease is critical.

Multiparametric or practical quantitative liver MRI: towards millisecond, fat fraction, kilopascal and function era.

INTRODUCTION: New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550-620 ms for 1.5 T and 700-850 ms for 3 T), T2, T2* (>20 ms), T1rho (40-50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients. Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed. Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.

Diffusion weighted magnetic resonance imaging of liver: Principles, clinical applications and recent updates.

Diffusion-weighted imaging (DWI), a functional imaging technique exploiting the Brownian motion of water molecules, is increasingly shown to have value in various oncological and non-oncological applications. Factors such as the ease of acquisition and ability to obtain functional information in the absence of intravenous contrast, especially in patients with abnormal renal function, have contributed to the growing interest in exploring clinical applications of DWI. In the liver, DWI demonstrates a gamut of clinical applications ranging from detecting focal liver lesions to monitoring response in patients undergoing serial follow-up after loco-regional and systemic therapies. DWI is also being applied in the evaluation of diffuse liver diseases such as non-alcoholic fatty liver disease, hepatic fibrosis and cirrhosis. In this review, we intend to review the basic principles, technique, current clinical applications and future trends of DW-MRI in the liver.

How many times should we repeat measuring liver stiffness using shear wave elastography?: 5-repetition versus 10-repetition protocols.

The purpose of this study is to evaluate whether a 5-repetition liver stiffness (LS) measurement as the standard protocol of shear wave elastography (SWE) is comparable to a conventional 10-repetition measurement protocol and to identify factors that influence the reliability of the 5-repetition protocol. A total of 346 patients (mean, 48.0years; range, 15-81years, M:F=192:154) who underwent SWE were enrolled. The median, first quartile, third quartile, and interquartile range divided by the median (IQR/M) of LS measurement were calculated and compared between 5-repetition and 10-repetition protocols. Subgroup analyses were also performed to identify factors associated with measurement reliability. The overall mean LS from the 10-repetition protocol was 7.97kPa, which was not significantly different from the mean LS of the 5-repetition protocol (7.91kPa; p=0.192). However, the third quartile and IQR/M values of the two groups were significantly different from each other (p=0.003 and <0.001). Subgroup analysis revealed that the 5-repetition results were significantly different from the 10-repetition results in the fatty liver and high LS subgroups. Therefore, the 5-repetition SWE measurement protocol can replace the conventional 10-repetition protocol, with the exception of patients with fatty liver disease or an LS value higher than 10kPa.

Determination of peripheral color signal density using contrast-enhanced color Doppler ultrasonography in diffuse liver disease.

PURPOSE: The study aimed to quantify hepatic vascular changes that accompany the development of chronic liver disease using contrast-enhanced color Doppler ultrasonography and histopathological examination. METHODS: A series of 62 patients with biopsy-proven chronic liver disease (31 chronic hepatitis, 31 liver cirrhosis) and 8 healthy controls were studied. Altogether, 22 livers (9 chronic hepatitis, 13 liver cirrhosis) obtained at surgery or autopsy were subjected to histopathological examination. Patients with cardiopulmonary disease or intrahepatic tumors were excluded. Intrahepatic color Doppler signals were scanned and counted at the liver surface in a 10 × 30 mm rectangle from liver segment V using color Doppler sonography (SSA 380 A) before and after contrast enhancement with SHU 508A (Levovist). Small arteries 30-1000 µm in diameter were counted on the histopathlogical specimen by microscopy. RESULTS: The number of color Doppler signals increased significantly after contrast enhancement in both patients and controls. The number of color Doppler signals was elevated before and after contrast enhancement when chronic liver disease was present, especially in cases of Child-Pugh grade C liver cirrhosis. Histologically, more arteries 30-125 µm in diameter were present in patients with chronic hepatitis than in those with liver cirrhosis, whereas more arteries ≦ 125 µm in diameter were present in patients with liver cirrhosis than in those with chronic hepatitis. CONCLUSION: Intrahepatic color Doppler signals are probably derived from peripheral arteries larger than 125 µm in diameter, and the signal density in these arteries increases with progression of the chronic liver disease.

Transjugular liver biopsy: indications, technique and results.

Transjugular liver biopsy is a safe, effective and well-tolerated technique to obtain liver tissue specimens in patients with diffuse liver disease associated with severe coagulopathies or massive ascites. Transjugular liver biopsy is almost always feasible. The use of ultrasonographic guidance for percutaneous puncture of the right internal jugular vein is recommended to decrease the incidence of local cervical minor complications. Semiautomated biopsy devices are very effective in obtaining optimal tissue samples for a precise and definite histological diagnosis with a very low rate of complication. The relative limitations of transjugular liver biopsy are the cost, the radiation dose given to the patient, the increased procedure time by comparison with the more common percutaneous liver biopsy, and the need of a well-trained interventional radiologist.