Value of magnetic resonance imaging in diffuse liver diseases

CLINICAL PROBLEM: Diffuse liver diseases show an increasing prevalence. The diagnostic gold standard of liver biopsy has several disadvantages. There is a clinical demand for non-invasive imaging-based techniques to qualitatively and quantitatively evaluate the entire liver. STANDARD RADIOLOGICAL METHODS: Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used. METHODICAL INNOVATIONS: Steatosis: chemical shift and frequency selective imaging, MR spectroscopy (MRS). Hemochromatosis: MR-based iron quantification. Fibrosis: MR elastography, diffusion, intravoxel incoherent motion (IVIM) and MR perfusion. PERFORMANCE/ACHIEVEMENTS/PRACTICAL RECOMMENDATIONS: T1-weighted in and opposed phase imaging is the clinically most frequently used MR technique to noninvasively detect and quantify steatosis. New methods for quantification that are not influenced by confounders like iron overload are under investigation. The most sensitive method to measure the fat content of the liver is MRS. As data acquisition and analysis remain complex and there is no whole organ coverage, MRS of the liver is not a routine method. With an optimized protocol incorporating T2* sequences, MRI is the modality of choice to quantify iron overload in hemochromatosis. Standard MR sequences cannot depict early stages of liver fibrosis. Advanced MR techniques (e.g. elastography, diffusion, IVIM and perfusion) for noninvasive assessment of liver fibrosis appear promising but their role has to be further investigated.     

Bildgebende Diagnostik der Leberzirrhose

For the diagnosis of liver cirrhosis ultrasound, computed tomography, magnetic resonance imaging, and angiography are recommended as imaging modalities. Ultrasound of the liver is used as a screening imaging tool in cases of patients suspicious for diffuse liver disease and is helpful in the term of follow-up examinations. Computed tomography is mainly performed to clarify the presence of liver disease detected by ultrasound. In this context, accurate examination of the vascular structures of the liver as well as extrahepatic situation, is of the essence. Diagnosis of diffuse liver disease and characterization of morphologic changes is improved using contrast-enhanced MR imaging with liver specific contrast media. Combined magnetic resonance imaging can provide comprehensive evaluation of cirrhosis. An improved detection rate and characterization of regenerating nodules can be achieved compared to imaging modalities such as ultrasound and computed tomography. MR imaging can be performed in a one-stop-technique using unenhanced and liver-specific-contrast-enhanced sequence protocols to evaluate the liver parenchyma itself, MR cholangiography to verify the bile duct system, and MR angiography to specify the vascular situation. This technique is the optimal protocol for diagnostic imaging in patients suffering from liver cirrhosis and the method of choice to reach the final diagnosis.     

Assessment of hepatic iron content using magnetic resonance imaging

Numerous studies over the past decade have shown that magnetic resonance imaging (MRI) has great potential for detecting and quantifying the distribution of iron in the body. With MRI, tissue iron is indirectly identified by the paramagnetic effects of iron on the shortening of water proton MR relaxation times. However, these effects are complex and involve a number of factors, such as tissue hydration, distribution of iron and water within the tissue, and the amount of iron loading within the iron storage molecules. A coherent understanding of how these factors influence the MRI signal is still lacking. The dependence on experimental conditions, such as magnet field strength, pulse sequences, and data acquisition parameters, further complicates iron quantification with MRI. To date, there is no generally accepted MRI approach available for clinical application. In this review, we first explain the basic MR relaxation mechanisms underlying the detection of iron with MRI. We then review the literature on empirical MRI studies of hepatic iron. Finally, we summarize the critical issues that need to be addressed to develop MRI techniques for non-invasive iron detection in the body.     

MRI of diffuse liver disease: characteristics of acute and chronic diseases

Diffuse liver disease, including chronic liver disease, affects tens of millions of people worldwide, and there is a growing need for diagnostic evaluation as treatments become more readily available, particularly for viral liver diseases. Magnetic resonance imaging (MRI) provides unique capabilities for noninvasive characterization of the liver tissue that rival or surpass the diagnostic utility of liver biopsies. There has been incremental improvement in the use of standardized MRI sequences, acquired before and after administration of a contrast agent, for the evaluation of diffuse liver disease and the study of the liver parenchyma and blood supply. More recent developments have led to methods for quantifying important liver metabolites, including lipids and iron, and liver fibrosis, the hallmark of chronic liver disease. Here, we review the MRI techniques and diagnostic features associated with acute and chronic liver disease.Magnetic resonance imaging (MRI) provides superior characterization of disease processes and masses in the liver compared with computed tomography (CT) (1) but requires attention to details regarding the optimal technique needed to achieve this relative performance. Routine MRI examination of the liver should include both single shot T2-weighted and breath-hold T1-weighted images (2), as well as gadolinium enhancement with the acquisition of multiple phases. The T1-weighted precontrast images must include in-phase and out-of-phase acquisitions to assess hepatic lipid or iron content. T1-weighted pre- and postgadolinium enhanced images are acquired using a fat-suppressed three-dimensional gradient-echo (3D GRE) sequence (3). These images are most commonly acquired in the axial plane with approximately 2 mm in-plane resolution and 2–3 mm resolution in the z-axis. Using various acceleration techniques, including parallel processing and under sampling, 3D GRE images covering the entire liver from the lung bases to below the kidneys can be acquired under 15 s during a single breath hold. Dynamically enhanced postgadolinium images are acquired to characterize tumors and diffuse liver disease. The timing of the arterial phase images is critical to providing unique diagnostic information for determining the perfusion characteristics of hepatic lesions and revealing hemodynamic changes related to active liver disease. The venous and delayed recirculation phase images, sometimes referred to as “equilibrium” phase images, are used for detecting other characteristic features delineating different tumor types and for grading hepatic fibrosis related to chronic liver disease. In chronic liver disease, dynamic postgadolinium images are critical for the detection and characterization of regenerative or dysplastic nodules and hepatocellular carcinoma. The same sequences that are useful for liver evaluation allow the comprehensive evaluation of all soft tissues of the abdomen and the depiction of most of the important diseases, and thus, they facilitate the use of a universal protocol for abdominal imaging.Various etiologies have been described for diffuse liver disease (4). This review article discusses acute and chronic liver disease processes in light of the MRI features and techniques that are used for the evaluation of diffuse liver diseases.     

CT and MRI of diffuse lobar involvement pattern in liver pathology

Focal, segmental, and diffuse liver pathologies have been described in the literature. This article describes a pattern in which liver pathology is confined to a lobe. This lobar pattern has not been described previously to our knowledge. Herein, we illustrate computed tomography (CT) and magnetic resonance imaging (MRI) findings of diffuse lobar involvement patterns in various liver conditions. Diffuse lobar involvement can be observed in benign (steatosis, hepatic iron overload, cholestasis, perfusion alterations, infarction, alveolar hydatid cysts, trauma, and hemangiomas) and primary malignant (hepatocellular carcinoma) pathologies. Diffuse lobar involvement in metastatic disease appears to be rare. Due in part to their potentially unusual appearances, the diagnosis of lobar pathologies using imaging can be challenging, and entities with lobar patterns can cause diagnostic confusion. Liver MRI can be used as a problem-solving tool for diffuse lobar pathologies detected on ultrasonography and CT. Inand out-of-phase MRI can help in the assessment of lobar fat accumulation.     

Moderne Leberbildgebung mit der MRT—aktuelle Trends und Zukunft

This contribution provides an overview and imparts basic knowledge on pertinent technical developments in magnetic resonance imaging (MRI) of the liver: 3D sequences, respiratory triggering, parallel imaging, and 3 Tesla (3T). 3D sequences can be used as T1-weighted (T1w) sequences for analyzing dynamics of contrast enhancement or as T2w sequences for MR cholangiography. Consistent improvements in respiratory triggering make it possible to obtain good image quality on T2w scans even in patients unable to hold their breath. Parallel imaging as a universal technique to accelerate image acquisition is particularly appropriate for MRI of the liver, and it has been shown that the reduced acquisition time is not achieved at the expense of image quality. Further progress in MRI of the liver can be expected with use of the 3T systems, but hitherto irrelevant problems must still be solved. Overall the innovations presented here, applied alone or in combination, facilitate rapid, robust, and high-quality MRI diagnostic assessment of the liver.     

Parametric exploration of the liver by magnetic resonance methods

MRI, as a completely noninvasive technique, can provide quantitative assessment of perfusion, diffusion, viscoelasticity and metabolism, yielding diverse information about liver function. Furthermore, pathological accumulations of iron and lipids can be quantified. Perfusion MRI with various contrast agents is commonly used for the detection and characterization of focal liver disease and the quantification of blood flow parameters. An extended new application is the evaluation of the therapeutic effect of antiangiogenic drugs on liver tumours. Novel, but already widespread, is a histologically validated relaxometry method using five gradient echo sequences for quantifying liver iron content elevation, a measure of inflammation, liver disease and cancer. Because of the high perfusion fraction in the liver, the apparent diffusion coefficients strongly depend on the gradient factors used in diffusion-weighted MRI. While complicating analysis, this offers the opportunity to study perfusion without contrast injection. Another novel method, MR elastography, has already been established as the only technique able to stage fibrosis or diagnose mild disease. Liver fat content is accurately determined with multivoxel MR spectroscopy (MRS) or by faster MRI methods that are, despite their widespread use, prone to systematic error. Focal liver disease characterisation will be of great benefit once multivoxel methods with fat suppression are implemented in proton MRS, in particular on high-field MR systems providing gains in signal-to-noise ratio and spectral resolution.     

Evaluation of iron overload by single voxel MRS measurement of liver T2

PURPOSE: To overcome the difficulty of poor signal-to-noise ratio of magnetic resonance imaging (MRI) in evaluating heavy iron overload by using a single voxel magnetic resonance spectroscopy (MRS) technique. MATERIALS AND METHODS: A single voxel STEAM pulse sequence with a minimum TE of 1.5 msec and a sampling volume of 36.6 cm(3) was developed and applied to 1/T2 measurement of the liver in 14 patients with thalassemia whose liver iron concentration was determined through biopsy. RESULTS: The iron level ranged from 0.23 to 37.15 mg Fe/g dry tissue with a median value of 18.06. In all cases, strong MR signals were obtained. 1/T2 was strongly correlated with the liver iron concentration (r = 0.95, P < 0.00005). CONCLUSION: The single voxel MRS measurement of T2 in liver iron overload overcomes the difficulty of lack of detectable signals in conventional MRI when the iron level is high. There is an excellent correlation between the iron level and 1/T2.     

Invited. Hepatitis,cirrhosis, and hepatoma

Virus hepatitis and liver cirrhosis are found at high incidence in Asia, and they require not only biochemical examination of blood but also subsequent imaging, because they are often complicated by hepatocellular carcinoma (HCC). It is, therefore, very important to know the specific appearances of hepatitis, liver cirrhosis, and HCC when we diagnose these diffuse liver diseases. Liver necrosis due to severe hepatitis is seen as high intensity on T2-weighted spin echo images. Regeneration is seen as low intensity on T2-weighted images. Morphologic and pathologic changes of cirrhotic liver are well demonstrated by MR imaging techniques. Fibrotic septum with inflammatory cell infiltration or rich pseudo bile duct show high intensity on T2-weighted images, and regenerating nodules shows low intensity. Gradient echo images show regenerating nodules with iron deposition as low-intensity nodules due to susceptibility artifact. MRI also has the potential to evaluate function of diffuse liver disease, cirrhosis, and hepatitis. MRI can visualize and diagnose HCC objectively. Dynamic MRI is very useful for diagnosing HCC. It is also applied for evaluation of effect after transcatheter arterial chemoembolization, because it shows enhancement only in the viable region at an arterial phase. MRI is less invasive and is thus an extremely important form of liver imaging.     

Ultrafast magnetic resonance scanning of the liver with echo-planar imaging

Echo-planar imaging (EPI) is a magnetic resonance imaging (MRI) technique which provides MR images in, typically, 50-100 ms. The potential of EPI as an imaging modality for the liver has been investigated in volunteers and patients with liver disease. Images with improved quality are presented. Obtained at a field strength of 0.52 Tesla, these true unaveraged snap-shot images have larger data arrays, comprising 128 X 128 pixels.     

Characterization of myocardial viability using MR and CT imaging

Cardiovascular magnetic resonance (MR) imaging is of proven clinical value for the noninvasive characterization of myocardial viability. Computed tomography (CT) is also being exploited for this indication. Examples of each of these imaging strategies for the assessment of myocardial viability will be provided in this review. Key MRI concepts and practical considerations such as customized MR imaging techniques and tailored imaging protocols dedicated to viability assessment are outlined with the primary focus on recent developments. Clinical applications of MR-based viability assessment are reviewed, ranging from rapid functional cine imaging to tissue characterization using T2-weighted imaging and T1-weighted late-contrast-enhanced imaging. Next, the merits and limitations of state-of-the-art CT imaging are surveyed, and their implications for viability assessment are considered. The final emphasis is on current trends and future directions in noninvasive viability assessment using MRI and CT.     

Quantification of liver iron with MRI: State of the art and remaining challenges

Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure, and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload and monitoring of iron‐reducing treatments. This article discusses the need for noninvasive assessment of liver iron and reviews qualitative and quantitative methods with a particular emphasis on magnetic resonance imaging (MRI). Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed. J. Magn. Reson. Imaging 2014;40:1003–1021 . © 2014 Wiley Periodicals, Inc .     

Assessment of motion gating strategies for mouse magnetic resonance at high magnetic fields

PURPOSE: To assess the performance of motion gating strategies for mouse cardiac magnetic resonance (MR) at high magnetic fields by quantifying the levels of motion artifact observed in images and spectra in vivo. MATERIALS AND METHODS: MR imaging (MRI) of the heart, diaphragm, and liver; MR angiography of the aortic arch; and slice-selective 1H-spectroscopy of the heart were performed on anesthetized C57Bl/6 mice at 11.75 T. Gating signals were derived using a custom-built physiological motion gating device, and the gating strategies considered were no gating, cardiac gating, conventional gating (i.e., blanking during respiration), automatic gating, and user-defined gating. Both automatic and user-defined modes used cardiac and respiratory gating with steady-state maintenance during respiration. Gating performance was assessed by quantifying the levels of motion artifact observed in images and the degree of amplitude and phase stability in spectra. RESULTS: User-defined gating with steady-state maintenance during respiration gave the best performance for mouse cardiac imaging, angiography, and spectroscopy, with a threefold increase in signal intensity and a sixfold reduction in noise intensity compared to cardiac gating only. CONCLUSION: Physiological gating with steady-state maintenance during respiration is essential for mouse cardiac MR at high magnetic fields.     

Magnetic resonance imaging of septic arthritis

Septic arthritis is a disabling and life-threatening disease that requires early diagnosis for optimal outcome. Although traditionally a clinical and laboratory diagnosis, some patients may be misdiagnosed and referred for magnetic resonance (MR) imaging. Therefore, radiologists need to be aware of the MR imaging findings of septic arthritis, its complications, and diagnostic pitfalls.     

Pitfalls in der CT bei diffusen Lebererkrankungen

CLINICAL/METHODICAL ISSUE: Misinterpretations in liver diagnostics could result in a false diagnosis, such as a parenchymatous damage or a false focal lesion. STANDARD RADIOLOGICAL METHODS: Computed tomography is a widely used diagnostic tool to visualize liver diseases. METHODICAL INNOVATIONS: Magnetic resonance imaging (MRI) is often used as a second diagnostic test to answer specific questions. PERFORMANCE: The more the condition of changes in liver parenchyma appearance in cross-sectional imaging is known the fewer mistakes will be made in the interpretation. Knowledge of these pitfalls helps to increase diagnostic accuracy. ACHIEVEMENTS: Magnetic resonance imaging could help to depict most of the pitfalls. PRACTICAL RECOMMENDATIONS: By looking at diffuse or focal liver diseases radiologists should be aware of perfusion patterns and structural changes of the liver parenchyma to make a correct diagnosis.     

Quantitation of total metastatic tumor volume in the rat liver: correlation of MR and histologic measurements.

Assessing tumor response to chemotherapy in the liver has always been difficult. Most investigators estimate tumor volume as either a product of the two perpendicular diameters of a tumor nodule, or, in animal studies, simply count surface tumor nodules. The authors evaluated magnetic resonance (MR) imaging as a technique for determining absolute tumor volume in the liver in an animal model. Specifically, histologic volumetric and MR imaging measurements of tumor and liver volumes were quantitatively compared over a wide range of tumor burdens in a rat model of hepatic metastasis of a colorectal carcinoma. Twenty-three rats were imaged, with two different section thicknesses used in each animal. Both section thicknesses showed highly significant correlations between MR and histologic measurements for both tumor and liver volumes (P less than .001). MR imaging may be useful for noninvasively quantifying tumor burden and temporal response of metastatic disease in the liver to novel antineoplastic regimens.     

Hepatobiliary MR imaging with gadolinium-based contrast agents

The advent of gadolinium-based "hepatobiliary" contrast agents offers new opportunities for diagnostic magnetic resonance imaging (MRI) and has triggered great interest for innovative imaging approaches to the liver and bile ducts. In this review article we discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the U.S., gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared toward optimizing workflow and imaging quality are also discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents and will stimulate the reader's pursuit of new applications for future benefit.     

Tissue-specific MR contrast agents

The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood-brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade.     

Magnetic resonance tomography of focal liver and spleen lesions. Experiences using ferrite, a new RES-specific MR contrast medium

Superparamagnetic iron oxide (ferrite), a novel, reticuloendothelial cell-specific contrast agent used for magnetic resonance imaging (MRI), was evaluated in the detection of liver and spleen tumors in animal models and in phase I and II clinical trials in 33 patients. The initial results obtained in experimental cancer models showed a dramatic improvement in tumor detection. Our first clinical trials confirmed the experimental results and showed that ferrite-enhanced MRI significantly (p less than 0.05) increases the detection of individual lesions. Furthermore, the threshold of detectable tumor size decreased significantly, to 3 mm, when standard MR spin echo imaging techniques were used.     

Focal manifestations of diffuse liver disease at MR imaging.

Detection and exclusion of focal liver lesions is especially difficult in patients with diffuse liver disease. Magnetic resonance (MR) imaging may be particularly valuable in these patients. By judicious comparison of appropriate pulse sequences, normal and hypertrophic liver may be distinguished from atrophic, neoplastic, or otherwise abnormal hepatic parenchyma. Chemical shift (lipid-sensitive) techniques allow definitive identification of fatty liver, including focal fatty infiltration or focal sparing. T2-weighted and T2*-weighted images allow identification of iron overload, depicting malignancies as focal masses without iron. Analysis of signal intensity and internal morphology allows confident distinction between regenerative nodules and hepatocellular carcinoma in most instances, and allows diagnosis of early carcinoma within regenerative nodules. MR imaging provides capabilities for noninvasive characterization of liver tissue beyond those available with other noninvasive modalities.