Liver function tests are commonly obtained in symptomatic and asymptomatic patients. Various overlapping lab patterns can be seen due to derangement of hepatocytes and bile ducts function. Imaging tests are pursued to identify underlying etiology and guide management based on the lab results. Liver function tests may reveal mild, moderate, or severe hepatocellular predominance and can be seen in alcoholic and nonalcoholic liver disease, acute hepatitis, and acute liver injury due to other causes. Cholestatic pattern with elevated alkaline phosphatase with or without elevated γ-glutamyl transpeptidase can be seen with various causes of obstructive biliopathy. Acute or subacute cholestasis with conjugated or unconjugated hyperbilirubinemia can be seen due to prehepatic, intrahepatic, or posthepatic causes. We discuss the initial and complementary imaging modalities to be used in clinical scenarios presenting with abnormal liver function tests. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

While there is evidence that iron overload disorders are associated with type 2 diabetes, the relationship between hepatic iron overload and prediabetes remains unclear. We aimed to investigate the association between hepatic iron overload, as assessed by magnetic resonance imaging (MRI), and different glucose intolerance states in the population-based Study.

We included data from 1622 individuals with MRI data, who did not have known type 2 diabetes (T2DM). Using an oral glucose tolerance testing, participants were classified as having isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) or previously unknown T2DM. Hepatic iron and fat contents were assessed through quantitative MRI. We undertook linear and multinomial logistic regression models adjusted for potential confounders and MRI-assessed hepatic fat content to examine the association of hepatic iron overload with different glucose intolerance states or continuous markers of glucose metabolism. MRI-assessed hepatic iron overload was positively associated only with both 2-h plasma glucose (β = 0.32; 95%CI 0.04-0.60) and the combined IFG + IGT category (relative risk ratio = 1.87; 95%CI 1.15-3.06). No significant associations were found between hepatic iron overload and other glucose intolerance states or biomarkers of glucose metabolism, independently of potential confounders.

MRI-assessed hepatic iron overload was associated with higher 2-h glucose concentrations and the combined IFG + IGT category, but not with other glucose intolerance states. Our findings suggest a weak adverse impact of hepatic iron overload on glucose metabolism, but further studies are needed to confirm these findings.

Hepatic dysfunction represents a wide spectrum of pathological changes, which can be frequently found in hepatitis, cholestasis, metabolic diseases, and focal liver lesions. As hepatic dysfunction is often clinically silent until advanced stages, there remains an unmet need to identify affected patients at early stages to enable individualized intervention which can improve prognosis. Passive liver function tests include biochemical parameters and clinical grading systems (e.g., the Child-Pugh score and Model for End-Stage Liver Disease score). Despite widely used and readily available, these approaches provide indirect and limited information regarding hepatic function. Dynamic quantitative tests of liver function are based on clearance capacity tests such as the indocyanine green (ICG) clearance test. However, controversial results have been reported for the ICG clearance test in relation with clinical outcome and the accuracy is easily affected by various factors. Imaging techniques, including ultrasound, computed tomography, and magnetic resonance imaging, allow morphological and functional assessment of the entire hepatobiliary system, hence demonstrating great potential in evaluating hepatic dysfunction noninvasively. In this article, we provide a state-of-the-art summary of noninvasive imaging modalities for hepatic dysfunction assessment along the pathophysiological track, with special emphasis on the imaging modality comparison and selection for each clinical scenario.

Proton density fat fraction (PDFF) is a validated biomarker of tissue fat quantification. However, validation has been limited to single-center or multi-center series using non-FDA-approved software. Thus, we assess the bias, linearity, and long-term reproducibility of PDFF obtained using commercial PDFF packages from several vendors.

Over 35 months, 438 subjects and 16 volunteers from a multi-center observational trial underwent PDFF MRI measurements using a 3-T MR system from one of three different vendors or a 1.5-T system from one vendor. Fat-water phantom sets were measured as part of each subject's examination. Manual region-of-interest measurements on the %fat image, then cross-sectional bias, linearity, and long-term reproducibility were assessed.

Three hundred ninety-two phantom measurements were evaluable (90%). Bias ranged from 2.4 to - 3.8% for the lowest to the highest weight %fat. Regression fits of PDFF against synthesis weight %fat showed negligible non-linear effects and a linear slope of 0.94 (95% confidence interval: 0.938, 0.947). We observed significant vendor (p < 0.001) and field strength (p < 0.001) differences in bias and longitudinal variability. When the results were pooled across sites, vendors, and field strengths, the estimated reproducibility coefficient was 6.93% (95% CI: 6.25%, 7.81%).

This study demonstrated good linearity, accuracy, and reproducibility for all investigated manufacturers and field strengths. However, significant vendor-dependent and field strength-dependent bias were found. While longitudinal PDFF measurements may be made using different field strength or vendor MR systems, if the MR system is not the same, based on these results, only PDFF changes ≥ 7% can be considered a true difference.

• Phantom fat fraction (PDFF) MRI measurements over 35 months demonstrated good linearity, accuracy, and reproducibility for the vendor systems investigated. • Non-linear effects were negligible (linear slope of 0.94) over 0-100% fat; however, significant vendor (p < 0.001) and field strength (p<0.001) differences in bias and longitudinal variability were identified. Bias ranged from 2.4 to - 3.8% for 0-100 weight% fat, respectively. • Measurement bias could affect the accuracy of PDFF in clinical use. As the reproducibility coefficient was 6.93%, only greater changes in % fat can be considered true differences when making longitudinal PDFF measurements on different MR systems.

From an invisible organ to one of the most explored non-invasively, the liver is, today, one of the cornerstones for current cross-sectional imaging techniques and minimally invasive procedures. After the achievements of US, CT and, most recently, MRI in providing highly accurate morphological and structural information about the organ, a significant scientific development has gained momentum for the last decades, coupling morphology to liver function and contributing far most to what we know today as precision medicine. In fact, dedicated tailor-made investigations are now possible in order to detect and, most of all, quantify physiopathological processes with unprecedented certitude. It is the intention of this review to provide a better insight to the reader of several functional imaging techniques applied to liver imaging. Contrast enhanced imaging, diffusion weighted imaging, elastography, spectral computed tomography and fat and iron assessment techniques are commonly performed clinically. Diffusion kurtosis imaging, magnetic resonance spectroscopy, T1 relaxometry and radiomics remain largely limited to advanced clinical research. Each of them has its own value and place on the diagnostic armamentarium and provide unique qualitative and quantitative information regarding the pathophysiology of diseases, contributing at a large scale to model therapeutic decisions and patient follow-up. Therefore, state-of-the-art liver imaging acts today as a non-invasive surrogate biomarker of many focal and diffuse liver diseases.

The aim of this study was to determine the optimal weighting factor (WF) for precise quantification using six-point interference Dixon fat percentage imaging by analyzing changes in WFs of fatty acid metabolites (FMs) in high-fat-induced fatty liver disease rat model.

Individual FM-related WFs were calculated based on concentration ratios of integrated areas of seven peak FMs with four phantom series. Ten 8-week-old male Sprague-Dawley rats were used for baseline quantification of fat in liver magnetic resonance imaging or magnetic resonance spectroscopy data. These seven lipid metabolites were then quantitatively analyzed. Spearman test was used for correlation analysis of different lipid proton concentrations. The most accurate WF for six-point interference Dixon fat percentage imaging was then determined.

The seven lipid resonance WF values obtained from magnetic resonance spectroscopy data for three different oils (oleic, linoleic, and soybean) were different from each other. In lipid phantoms, except for the phantom containing oleic acid, changes in FP values were significantly different when WFs were changed in six-point interference Dixon fat percentage image. The seven lipid resonance WF values for the nonalcoholic fatty liver animal model were different from human subcutaneous adipose tissue lipid WF values.

WF affected the calculation of six-point interference Dixon-based fat percentage imaging value in phantom experiment. If WF of liver parenchyma FM which is specific to each liver disease is applied, the accuracy of six-point interference Dixon fat percentage imaging can be further increased.

The prevalence of nonalcoholic fatty liver disease has been continuously rising over the last three decades and is projected to become the most common indication for liver transplantation in the near future. Its pathophysiology and complex interplay with diabetes and the metabolic syndrome are not as yet fully understood despite growing scientific interest and research. Modern imaging techniques offer significant assistance in this field by enabling the study of the liver noninvasively and evaluation of the degree of both steatosis and fibrosis, and even in attempting to diagnose the presence of inflammation (steatohepatitis). The derived measurements are highly precise, accurate and reproducible, performing better than biopsy in terms of quantification. In this article, these imaging techniques are overviewed and their performance regarding diagnosis, stratification and monitoring are evaluated. Their expanding role both in the research arena and in clinical practice along with their limitations is also discussed.

The diagnostic gold standard for nonalcoholic fatty liver disease is an invasive biopsy. Noninvasive Cartesian MRI fat quantification remains limited to a breath-hold (BH). In this work, a novel free-breathing 3D stack-of-radial (FB radial) liver fat quantification technique is developed and evaluated in a preliminary study.

Phantoms and healthy subjects (n = 11) were imaged at 3 Tesla. The proton-density fat fraction (PDFF) determined using FB radial (with and without scan acceleration) was compared to BH single-voxel MR spectroscopy (SVS) and BH 3D Cartesian MRI using linear regression (correlation coefficient ρ and concordance coefficient ρ_c ) and Bland-Altman analysis.

In phantoms, PDFF showed significant correlation (ρ > 0.998, ρ_c  > 0.995) and absolute mean differences < 2.2% between FB radial and BH SVS, as well as significant correlation (ρ > 0.999, ρ_c  > 0.998) and absolute mean differences < 0.6% between FB radial and BH Cartesian. In the liver and abdomen, PDFF showed significant correlation (ρ > 0.986, ρ_c  > 0.985) and absolute mean differences < 1% between FB radial and BH SVS, as well as significant correlation (ρ > 0.996, ρ_c  > 0.995) and absolute mean differences < 0.9% between FB radial and BH Cartesian.

Accurate 3D liver fat quantification can be performed in 1 to 2 min using a novel FB radial technique. Magn Reson Med 79:370-382, 2018. © 2017 International Society for Magnetic Resonance in Medicine.