Safety of magnetic resonance imaging contrast agents.

Many of the MR examinations performed in the world each year are accompanied by administration of one of these frequently used intravenous contrast agents: Magnevist, Omniscan, and ProHance. Accordingly, MR practitioners must understand the basic pharmacokinetics, side effects, and the potential for adverse events for these contrast agents. Additionally, MR practitioners must know how to manage side effects and adverse events that may occur in association with the administration of contrast agents. Notably, the use of MR imaging contrast agents in special patient populations must be understood. This article discusses each of these important issues.     

Water diffusion and exchange as they influence contrast enhancement

The contrast-enhanced magnetic resonance imaging (MRI) signal is rarely a direct measure of contrast concentration; rather it depends on the effect that the contrast agent has on the tissue water magnetization. To correctly interpret such studies, an understanding of the effects of water movement on the magnetic resonance (MR) signal is critical. In this review, we discuss how water diffusion within biological compartments and water exchange between these compartments affect MR signal enhancement and therefore our ability to extract physiologic information. The two primary ways by which contrast agents affect water magnetization are discussed: (1) direct relaxivity and (2) indirect susceptibility effects. For relaxivity agents, for which T1 effects usually dominate, the theory of relaxation enhancement is presented, along with a review of the relevant physiologic time constants for water movement affecting this relaxation enhancement. Experimental issues that impact accurate measurement of the relaxation enhancement are discussed. Finally, the impact of these effects on extracting physiologic information is presented. Susceptibility effects depend on the size and shape of the contrast agent, the size and shape of the compartment in which it resides, as well as the characteristics of the water movement through the resulting magnetic field inhomogeneity. Therefore, modeling of this effect is complex and is the subject of active study. However, since susceptibility effects can be much stronger than relaxivity effects in certain situations, they may be useful even without full quantitation.     

Contrast agents for MR imaging of the liver

Imaging of the liver is performed most often to detect and characterize focal liver lesions. MR imaging has been the method of choice to assess focal liver lesions accurately. Nonspecific intravenous contrast agents have been used for routine abdominal MR imaging protocols including liver imaging. Over the last 10 to 15 years new contrast agents have been developed that combine the excellent contrast resolution of MR imaging with improved tissue specificity. This article reviews various contrast agents that are in clinical use for liver MR imaging and discusses their potential clinical role.     

MRI of tumor angiogenesis

Angiogenesis has long been established as a key element in the pathophysiology of tumor growth and metastasis. Increasingly, new molecularly targeted antiangiogenic drugs are being developed in the fight against cancer. These drugs bring with them a need for an accurate means of diagnosing tumor angiogenesis and monitoring response to treatment. Imaging techniques can offer this in a noninvasive way, while also providing functional information about the tumor. Among the many clinical imaging techniques available, MRI alone can provide relatively good spatial resolution and specificity, without ionizing radiation and with limited side effects. Arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging techniques can be employed to confer indirect measures of angiogenesis, such as blood flow and blood volume, without the need for external contrast agents. Dynamic contrast-enhanced (DCE)-MRI is rapidly emerging as a standard method for directly measuring angiogenesis during angiogenesis-inhibitor drug trials. As macromolecular MR contrast agents become available, they will inevitably be utilized in the assessment of tumor perfusion and vessel permeability. Meanwhile, technological advances have made imaging at a molecular level a possibility. They have brought the potential to directly target MR contrast agents to markers of angiogenesis, such as the alpha(v)beta(3) integrin. Before this is used clinically, however, substantial gains in sensitivity brought about by improved coils, pulse sequences, and contrast agents will be needed. Herein we discuss the techniques currently available for MRI of angiogenesis, along with their respective advantages and disadvantages, and what the future holds for this evolving field of imaging.     

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.     

Value of MR contrast media in image-guided body interventions

In the past few years,there have been multiple advances in magnetic resonance (MR) instrumentation,in vivo devices,real-time imaging sequences and interventional procedures with new therapies.More recently,interventionists have started to use minimally invasive image-guided procedures and local therapies,which reduce the pain from conventional surgery and increase drug effectiveness,respectively.Local therapy also reduces the systemic dose and eliminates the toxic side effects of some drugs to other organs.The success of MR-guided procedures depends on visualization of the targets in 3D and precise deployment of ablation catheters,local therapies and devices.MR contrast media provide a wealth of tissue contrast and allows 3D and 4D image acquisitions.After the development of fast imaging sequences,the clinical applications of MR contrast media have been substantially expanded to include pre-during-and post-interventions.Prior to intervention,MR contrast media have the potential to localize and delineate pathologic tissues of vital organs,such as the brain,heart,breast,kidney,prostate,liver and uterus.They also offer other options such as labeling therapeutic agents or cells.During intervention,these agents have the capability to map blood vessels and enhance the contrast between the endovascular guidewire/catheters/devices,blood and tissues as well as direct therapies to the target.Furthermore,labeling therapeutic agents or cells aids in visualizing their delivery sites and tracking their tissue distribution.After intervention,MR contrast media have been used for assessing the efficacy of ablation and therapies.It should be noted that most image-guided procedures are under preclinical research and development.It can be concluded that MR contrast media have great value in preclinical and some clinical interventional procedures.Future applications of MR contrast media in image-guided procedures depend on their safety,tolerability,tissue specificity and effectiveness in demonstrating success of the interventions and therapies.     

Contrast material for computed tomography and magnetic resonance imaging of the gastrointestinal tract

Various contrast agents are applied in both CT and MR imaging to improve the detection as well as the differentiation of focal liver lesions. In detecting hepatocellular carcinoma, the accuracy of Lipiodol-enhanced CT is comparable to that of CT during arterial portography. Tissue-specific contrast agents for the liver are superparamagnetic iron oxide particles, which are characterized by uptake in the reticuloendothelial system, and the paramagnetic hepatobiliary contrast agent manganese (II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate). Both substances have the potential for markedly improving the detection of malignant liver tumors. The already good differentiation of focal hepatic lesions on plain MR images can be further improved by dynamic gadolinium diethylenetriamine penta-acetic acid-enhanced MR imaging. In the diagnosis of bile duct disorders, contrast-enhanced CT continues to be the method of choice. Water applied as a gastrointestinal contrast agent improves the staging of rectal carcinoma by CT. The development of suitable orally applied gastrointestinal contrast agents has now also improved the differentiation of the intestine from other abdominal structures on MR images, and this will lead to a general improvement of abdominal MR imaging.     

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.     

Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging

Superparamagnetic iron oxide MR imaging contrast agents have been the subjects of extensive research over the past decade. The iron oxide particle size of these contrast agents varies widely, and influences their physicochemical and pharmacokinetic properties, and thus clinical application. Superparamagnetic agents enhance both T1 and T2/T2* relaxation. In most situations it is their significant capacity to reduce the T2/T2* relaxation time to be utilized. The T1 relaxivity can be improved (and the T2/T2* effect can be reduced) using small particles and T1-weighted imaging sequences. Large iron oxide particles are used for bowel contrast [AMI-121 (i.e. Lumirem and Gastromark) and OMP (i.e. Abdoscan), mean diameter no less than 300 nm] and liver/spleen imaging [AMI-25 (i.e. Endorem and Feridex IV, diameter 80-150 nm); SHU 555A (i.e. Resovist, mean diameter 60 nm)]. Smaller iron oxide particles are selected for lymph node imaging [AMI-227 (i.e. Sinerem and Combidex, diameter 20-40 nm)], bone marrow imaging (AMI-227), perfusion imaging [NC100150 (i.e. Clariscan, mean diameter 20 nm)] and MR angiography (NC100150). Even smaller monocrystalline iron oxide nanoparticles are under research for receptor-directed MR imaging and magnetically labeled cell probe MR imaging. Iron oxide particles for bowel contrast are coated with insoluble material, and all iron oxide particles for intravenous injection are biodegradable. Superparamagnetic agents open up an important field for research in MR imaging.     

Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes

The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of vulnerable plaque and may allow for monitoring the efficacy of antiatherosclerotic therapies. In this review we focus on MR imaging strategies for the detection and evaluation of atherosclerotic plaques and their composition. We highlight recent advancements in the development of MR pulse sequences, computer image analysis, and the use of commercially available MR contrast agents, such as gadopentic acid (Gd-DTPA), for plaque characterization. We also discuss molecular imaging strategies that are currently being used to design specific imaging probes targeted to biochemical and cellular markers of atherosclerotic plaque vulnerability.     

Safety of approved MR contrast media for intravenous injection

In the last 10 years, the use of intravenous contrast media in magnetic resonance (MR) has become well-established clinical practice. Contrast media provide critical additional diagnostic information in many instances. The gadolinium chelates constitute the largest group of MR contrast media and are considered to be very safe. These agents are thought to be safer than nonionic iodinated contrast agents. Unlike x-ray agents, the gadolinium chelates are not nephrotoxic. Minor adverse reactions, including nausea (1%-2% for all agents) and hives (<1% for all agents), occur in a very low percent of cases. Health care personnel should be aware of the (extremely uncommon) potential for severe anaphylactoid reactions in association with the use of MR contrast media and be prepared should complications arise. The four gadolinium chelates currently available worldwide, gadopentetate dimeglumine, gadoteridol, gadodiamide, and gadoterate meglumine, cannot be differentiated on the basis of adverse reactions. Far fewer patients have been examined to date with the two other agents that have widespread approval, mangafodipir trisodium and ferumoxides. These latter two agents are considered to be very safe but have a higher percentage of associated adverse reactions (7%-17% with mangafodipir trisodium and 15% with ferumoxides). This review discusses the safety issues involved with administration of intravenous contrast media in MR imaging, focusing on the six agents (four gadolinium chelates, one manganese chelate, and the last a large iron particle) with widespread use world-wide.     

MRA for diagnosis of venous thromboembolism.

Direct imaging of pulmonary embolism (PE) and deep vein thrombosis (DVT) with CT, and potentially with MR, will continue to replace V/Q scintigraphy. Venous imaging with MR far detecting DVT is used in a few centers, and their published accuracy figures are impressive. Recent studies of MR pulmonary angiography for PE reported that sensitivity of MRA was 85-100%, specificity 95-96%, but this data must be confirmed in other centers and patient populations. MR has advantages compared with CT, which make it worthwhile to continue MR development. Ionizing radiation and iodinated contrast material are not used. Imaging the pulmonary arteries and then imaging whichever venous region is of clinical interest is practical in a single examination. Repeated examinations can be performed safely. New contrast materials will facilitate the practicality and accuracy of the MR technique and perfusion imaging may increase sensitivity. MR also has disadvantages compared with CT. It does not image effectively the non-vascular compartment of the lungs. It is more expensive, patient monitoring is more cumbersome, and a routine technique, which embodies all of MR's potential advantages, has not been packaged and tested. Accordingly, helical CT is a realistic option in clinical management of patients with suspected PE in most centers, while clinical application of MR is limited to centers with appropriate MR expertise and technology. However, MR has a number of fundamental characteristics that make it a potentially ideal modality for evaluating patients with suspected acute venous thromboembolic disease and further clinical research with MRA is warranted.     

Leo J. Rigler lecture. MR imaging of the liver

Recent technical and clinical advances in MR of the liver are reviewed with special reference to the role of MR as a primary screening technique for detection of space-occupying lesions, especially metastases. The major current problem in upper abdominal MR imaging is physiologic motions, and this appears to have been effectively solved by newly introduced pulse-sequence and timing-parameter strategies. Short-TR/TE spin-echo sequences with extensive signal averaging and heavy T1-weighting produce images with exceptional anatomic detail and liver-cancer contrast differences. With this sequence superior sensitivity for liver-cancer detection has been shown in quantitative signal-difference to noise comparisons with other pulse sequences and in clinical comparisons with CT. MR discovered 14% more individual metastases and 3% more patients with liver cancer than CT in a blinded comparative study of 142 patients undergoing both exams. MR also showed greater specificity (98%) than CT (91%) in distinguishing patients without liver metastases. Differentiation of hemangioma from metastases was possible with greater than 90% specificity by using heavily T2-weighted sequences. Use of a fast-scan, gradient-recalled echo technique can also produce good-quality, multislice, T1-weighted studies of the liver in 20 sec--a breath-hold. MR contrast agents (such as gadolinium-DTPA and reticuloendothelial-system-specific, superparamagnetic ferrite-iron-oxide particles) offer further promise for enhanced sensitivity for liver-cancer detection. When optimal pulse sequences are employed, MR can now be appropriate as a primary screening method for detecting liver neoplasms.     

Equipment requirements to facilitate contrast-enhanced MR imaging.

During the past decade, MR equipment and imaging techniques have experienced unprecedented development. Significant improvements have been made in image quality, enhancing conventional contrast agent studies. In addition, the development of new applications, such as MR angiography, has expanded the role of existing agents. A major benefit for contrast agent research has been the development of ultrafast MR imaging. This ability to provide information on contrast agent dynamics will aid in the detection and characterization of neoplastic and other disease states. While the gradient-echo techniques may provide adequate temporal resolution for many applications, echo planar imaging will enable the assessment of perfusion for an entire organ, which is critical in the heart or when the location of the pathology is unknown a priori. It is also likely that continued development in MR contrast agents will have a synergistic impact on pulse sequences, e.g., MR diffusion imaging. The growth in functional MR imaging will be based in large measure on the continued interactive development of imaging strategies and magnetopharmaceutials.     

MR contrast agents: an overview

In this article an overview of current and potential MR contrast agents is given. The mechanism of action of contrast agents and their relationship to both T1 and T2 relaxation are explored. Both paramagnetic and superparamagnetic substances are considered. Various physical states of these materials, including small ionic, lipophilic, and macromolecular forms are explored as possible contrast agents. Several clinical examples are given and speculation is made about the future potential of MR contrast agents.     

Neuroradiology back to the future: spine imaging

Although radiography of the spine began shortly after Roentgen's discovery in 1895, there was little written in the medical literature about spine imaging until nearly 25 years later with the development of myelography, first by using air and then a variety of positive contrast agents. The history of spine imaging before CT and MR imaging is, in large part, a history of the development of contrast agents for intrathecal use. The advent of CT and, more important, MR imaging revolutionized spine imaging. The spinal cord and its surrounding structures could now be noninvasively visualized in great detail. In situations in which myelography is still necessary, advances in contrast agents have made the procedure less painful with fewer side effects. In this historical review, we will trace the evolution of spine imaging that has led to less invasive techniques for the evaluation of the spine and its contents and has resulted in more rapid, more specific diagnosis, therapy, and improved outcomes.     

Status and development of new clinical contrast media for MR diagnosis of liver diseases]

MR contrast agents are developed for pharmaceutical manipulation of tissue signal intensities. Today it is widely recognized that MR contrast agents will play an increasingly important role in MR imaging of the liver. Contrast-enhanced MR-imaging allows to obtain simultaneously dynamic physiologic information and high anatomic detail. Up to now three major classes of MR contrast agents are available for clinical MR-imaging of the liver. These include paramagnetic perfusion agents, hepatobiliary agents, and super-paramagnetic RES-specific iron oxide particles. A fourth class of contrast agents now in use for animal experiments includes ultra-small super-paramagnetic particles which can be targeted to extra-reticuloendothelial structures such as asialoglycoprotein receptors of hepatocytes. In this article, we review recent advances in the development of MR contrast media and the clinical status of contrast-enhanced MR imaging of the liver.     

Allergic reactions to iodinated contrast media: premedication considerations for patients at risk

The objectives of this article are to review allergy-type reactions to iodinated contrast media and the protocols utilized to prevent or reduce the occurrence of these adverse reactions in high-risk patients. We will begin by discussing the types or classifications of the adverse reactions to iodinated contrast media. We will then discuss reaction mechanisms, identify the patients at highest risk for adverse reactions, and clarify common misperceptions about the risk. Finally, we will discuss the actions of the medications used to help reduce or prevent allergy-type reactions to iodinated contrast media, the protocols used to help reduce or prevent contrast reactions in high-risk patients, and the potential side effects of these medications. We will also discuss the high-risk patient who has received premedication due to a prior index reaction and discuss the risk of having a subsequent reaction, termed “breakthrough reaction.” Identifying patient at high risk for an “allergy-type” reaction to contrast media is an essential task of the radiologist. Prevention of or reduction of the risk of an adverse reaction is critical to patient safety. If an examination can be performed without contrast in a patient at high risk for an allergy-type reaction, it may be appropriate to avoid contrast. However, there are situations where contrast media is necessary, and the radiologist plays a vital role in preventing or mitigating an allergy-type reaction.     

Common injuries related to weightlifting: MR imaging perspective

Weightlifting has evolved to become a ubiquitous form of exercise. Resistance training has been shown to have beneficial effects on both muscle and osseous maintenance and development. Competitive weightlifting sports continue to enjoy tremendous popularity, with participants striving to establish new standards in performance and more demanding personal goals. Thus, it is not surprising that we have also seen an increase in injuries related to weightlifting. Many of these injuries are radiographically occult and are best suited for evaluation by magnetic resonance (MR) imaging because many involve the soft tissues. In this article, we discuss some of the factors that contribute to these injuries and address the mechanisms of injury and the MR imaging manifestations of the more common injuries.