Practical Considerations in Magnetic Resonance Imaging Contrast Studies

Terry Duggan-Jahns, RT(R)(CT)(MR)(M)

  ^*Manager, Outpatient Diagnostic Imaging, St. Joseph Medical Center, Tacoma, Washington.
  Address correspondence to: Terry Duggan-Jahns, RT(R)(CT)(MR)(M), Manager, Outpatient Diagnostic Imaging, St. Joseph Medical Center, 1717 South J Street, Tacoma, WA 98405. E-mail: tdugganjahns@mac.com.

Disclosure Statement: Ms Duggan-Jahns reports having no significant financial or advisory relationships with corporate organizations related to this activity.

ABSTRACT

Magnetic resonance imaging (MRI) represents an important advance in clinical diagnostics and continues to demonstrate wider applicability through innovations in systems hardware and software. In addition, contrast media specifically developed for use in MRI studies have resulted in new applications for MRI contrast studies that can offer additional diagnostic information and prove less invasive than other diagnostic tools used in clinical practice. MRI technologists who encounter MRI contrast in daily practice require a detailed knowledge of the different tissue interactions with the MRI field and the proper MRI sequences used to obtain useful diagnostic images with different organ systems. MRI contrast studies in a variety of clinical applications are presented in this article, with special attention to proper MRI sequences based on the study performed, different classes of contrast agents, and important safety considerations with MRI contrast media.

Introduction
Magnetic resonance imaging (MRI) is an important imaging modality that provides a relatively safe, noninvasive alternative to other imaging techniques. Although the feasible diagnostic applications of MRI were once limited, advances in both MRI systems hardware and software continue to expand the applicability of this modality in daily diagnostic practice. In addition, MRI contrast studies, with contrast media specifically designed for use in conjunction with MRI, are now routinely available in some clinical applications but require an advanced understanding of the proper system sequences and dosing considerations needed to effectively obtain useful images. In this article, the practical application of MRI contrast will be discussed, including sequences used in these studies, contrast agents used for imaging of different organ systems, contrast dosing guidelines, and safety considerations with the administration of MRI contrast media.

Factors that Affect MRI Contrast
Contrast is one of the major concerns in medical imaging, and determines the ability to distinguish and characterize certain structures with sharpness and accuracy from one another. All clinical diagnostic images must be able to demonstrate contrast between normal anatomical features and between anatomy and pathology. One of the main advantages of MRI compared with other imaging modalities is its excellent soft tissue discrimination. A successful MRI study results in an image that exhibits sufficient contrast between areas of high signal (white regions) and areas of low signal (dark regions). There are numerous factors that control or influence MRI contrast and can generally be divided into intrinsic and extrinsic factors. Intrinsic contrast factors are those that cannot be changed because they are inherent to the body's tissues. Extrinsic factors, meanwhile, are those that can be changed through adjustments in the MRI process. However, many extrinsic factors in MRI contrast can affect intrinsic factors and image quality. The complexity of the interactions between intrinsic and extrinsic factors requires well-trained MRI technologists who are aware of these factors and are able to manipulate them successfully during the diagnostic process. Intrinsic and extrinsic factors affecting MRI contrast are listed in Table 1.¹

One of the main advantages of MRI is the ability to change contrast by choosing special pulse sequences and pulse sequence parameters. However, minor changes in these factors can cause severe changes in contrast. Contrast-to-noise ratio (CNR) is defined as the difference in the signal-to-noise ratio (SNR) between 2 adjacent areas. The CNR is probably the most critical factor affecting image quality because it directly determines one's ability to distinguish areas of high signal from areas of low signal. The purpose of administrating contrast agents is to increase the CNR between pathology and normal tissue.⁴ Other important factors in image quality are spatial resolution and SNR. Spatial resolution is the ability to distinguish between 2 points as separate and distinct, and is controlled by voxel size. A smaller voxel size results in better spatial resolution. SNR is the ratio of the amplitude of the signal received to the average of the noise.² The noise is generated by the presence of the patient in the magnet and the background electrical noise of the system.

Other parameters dictated in the performance of an MRI study can also substantially affect image contrast. For instance, the time to repeat (TR; time between pulse sequences, or time interval between successive 180° pulses [or successive 90° pulse]); the time to echo (TE; the length of time the signal is measured); and flip angle also influence image contrast and SNR as well as overall image quality. Overall, studies performed with greater SNR result in increased image quality and resolution.

Interpretation of MRIs is also based on an analysis of tissue contrast yielded with the study. Relaxation times or signal weightings, the time that it takes for a magnetic spin to return to equilibrium, are fixed properties for different tissues subjected to specific magnetic field strengths. The T1 signal weighting parameter is called the longitudinal relaxation time because it refers to realignment along the z-axis. The T2 signal weighting parameter refers to realignment along the xy-axis, and the T2* signal weighting refers to xy-axis realignment while taking the relative homogeneity of the external magnetic field into account. Each distinct tissue type also has a unique proton density (PD) that affects tissue contrast and image interpretation. As each tissue type exhibits different T1, T2, and PD parameters, image contrast manipulations can be characterized as T1 weighted, T2 weighted, or PD weighted.³ To ensure proper image contrast and quality, MRI technology professionals performing MRI need to be aware of the proper sequences used when performing studies of different tissue types.

Practical Considerations: MRI Sequence Strategies that Influence Contrast
There are general characteristics of different tissue types that guide the use of proper MRI sequences to achieve sufficient image contrast. For instance, fat tissue exhibits the shortest T1 and has the steepest T1 recovery, but has an intermediate T2. Water, meanwhile, has the longest T1 and the slowest T1 recovery. Water also has a long T2, and therefore exhibits a very shallow T2 decay. Solid tissue has an intermediate T1 and a short T2, and therefore exhibits fairly rapid signal decay.

T1-Weighted Studies
T1-weighted tissue contrast depends predominately on the differences in the T1 times between fat and water. The TR controls how far each vector can recover before the excitation by radiofrequency pulse. To achieve T1-weighted images, the TR must be short enough so that either fat or water has time to return to equilibrium. TR controls the amount of T1 weighting. A short TR enhances T1 contrast, whereas a long TR reduces the T1 effect. To achieve successful T1-weighted imaging, the parameters would be a short TR and a short TE.

T2-Weighted Studies
The T2 characteristics of a tissue are determined by how fast the proton spins in that tissue dephase. If they dephase rapidly, a short T2 is exhibited. If the protons in the tissue tend to dephase more slowly, a longer T2 occurs. TE controls the amount of T2 weighting. For T2 weighting, the TE must be long. To achieve T2-weighted imaging, the parameters would therefore be a long TR and a long TE.

PD-Weighted Studies
The proton imaging characteristics of a tissue are dependent upon the differences in the number of protons per unit volume in the patient. In order to achieve PD weighting, the effects of T1 and T2 contrast must be diminished so that PD weighting is dominant. A long TR allows for both fat and water to recover to equilibrium and therefore diminishes T1 weighting. A short TE does not give water or fat time to decay, and therefore diminishes T2 weighting. Therefore, to achieve proper PD weighting imaging, the necessary parameters are a long TR and a short TE.

Resulting Images
The signal in MRI is high or low (bright or dark) depending on the pulse sequence used and the type of tissue in the imaged region of interest. In T1-weighted imaging, dark areas are indicative of increased water due to possible edema, tumor, infarction, inflammation, infection, or hemorrhage (hyperacute or chronic), depending on the tissue studied. Bright areas in T1-weighted imaging can be indicative of a variety of factors, depending on the tissue under analysis and the nature of MRI study. For instance, these bright areas could reflect fat, subacute hemorrhage, melanin, or protein-rich fluid; slow-moving blood; or a laminar necrosis of a cerebral infarct. Bright areas in T1-weighted images could also illustrate the uptake of a paramagnetic substance, such as gadolinium, manganese, or copper, from the contrast agent or other bodily processes.

In T2-weighted imaging, dark regions reflect areas of low PD, including calcifications or fibrous tissues, flow void, or protein-rich fluid. These areas could also indicate the presence of paramagnetic substances, including deoxy-hemosiderin, intracellular methemoglobin, iron, ferritin, hemosiderin, or melanin. Unlike T1-weighted imaging, bright areas in T2-weighted images can often reflect an increase in water due to edema, tumor, infarction, inflammation, infection, or hemorrhage (hyperacute or chronic). Also, bright areas can be consistent with extracellular methemoglobin accumulation in subacute hemorrhage. Figure 1 illustrates the differences between spinal studies with T1- and T2-weighted imaging.

Brain imaging results in specific bright and dark regions depending on whether T1- or T2-weighted imaging is used. Cerebrospinal fluid appears dark on T1-weighted images and bright on T2-weighted images. Meanwhile, gray matter appears with an intermediate level of contrast (not bright or dark) in both T1- and T2-weighted studies. Finally, white matter appears as bright in T1-weighted studies and dark on T2-weighted studies.

Contrast Media in MRI
In the early years of clinical MRI use, it was believed that the natural contrast between different soft tissues would avoid the need for contrast media. However, similar to findings in computed tomography (CT), radiologic technologists and radiologists soon determined that the signal differences between different tissues (ie, the contrast in the MRI) could be profoundly improved by different contrast media. In fact, the addition of contrast media modalities to MRI has revolutionized the field. MRI contrast agents increase the intrinsic contrast between vascularized and nonvascularized tissue. The first MRI contrast agent was based on a paramagnetic gadolinium ion inside the chelate diethylenetriamine penta-acetic acid (gadopentetate dimeglumine or Gd-DTPA). After Gd-DTPA became commercially available and allowed for MRI contrast studies, the quality of MRI studies became equal to or better than CT in certain applications. The addition of contrast medium to an imaging study increases the conspicuity of pathologic lesions. Therefore, contrast MRI is especially useful in imaging primary and secondary tumors, abscesses, infection, and inflammation. Likewise, contrast MRI is also helpful in improving the visualization of arterial anatomy, venous anatomy, and vascular pathology.

Basic Principles of MRI Contrast Agents
When contrast agents are used in CT, the contrast enhancement is directly related to the concentration of the agent. Meanwhile, contrast agents used in MRI have effects on the relaxation rate of the tissue that are directly visualized in the resulting images. MRI contrast agents are therefore categorized as either T1 or T2 agents. T1 agents, or positive enhancement agents, are paramagnetic substances with a large magnetic moment that shorten the T1 relaxation times of protons in tissues that absorb the contrast agent. This process results in an increase in signal intensity (resulting in enhanced brightness) that is visualized on T1-weighted images. T1 paramagnetic images also shorten the T2 and T2* relaxation of tissue protons. T2 agents, or negative enhancement agents, are supermagnetic substances, such as iron oxides, that shorten T2 decay times and thus decrease signal intensity (resulting in enhanced darkness) on T2-weighted images.

Magnetic resonance imaging contrast agents can be further divided into different classes depending on the type of agent used and the route of administration (Table 2).⁴ There are now 5 major categories of MRI contrast agents, including nonspecific extracellular agents, hepatocyte-specific agents, reticuloendothelial system (RES)-specific agents, lymph node-specific agents, and oral contrast agents for gastrointestinal imaging.

Nonspecific Extracellular Agents
Most T1 contrast agents are derived from paramagnetic materials that are characterized by the presence of unpaired electrons. The majority of these are nonspecific extracellular agents. Gadolinium chelates are the most widely used nonspecific extracellular agents. Gadolinium chelates approved by the US Food and Drug Administration (FDA) for intravenous (IV) administration are summarized in Table 3. The recommended effective dosage of Gd-DTPA is 0.1 mmol/kg body weight, with a maximum dose of 20 mL. The gadolinium chelate gadoteridol (Gd-HP-DO3A) has been approved for doses of up to 0.3mL/kg, or 3 times the recommended dose of Gd-DTPA, if an initial dosage of 0.1 mmol/kg yields negative or equivocal images and a poorly enhanced lesion is suspected.⁵ The lethal dose of gadolinium found in rats, which is never approached in the clinical setting, has been determined to be 10 mmol/kg.²

Hepatocyte-Specific Agents
Several nonspecific, passive targeting IV contrast compounds have been introduced for use in liver imaging studies. In general, these compounds target either the vascular structures within the liver, hepatocytes, or the RES. Unlike other organs, the liver receives a dual blood supply. The portal vein supplies the liver with 80% of its blood supply, but only 40% of its oxygen supply. The majority of the liver's oxygen supply comes from the hepatic artery, which is the other source of blood for the liver. Liver hepatocytes perform individual functions associated with the liver, including the digestion and catabolism of lipoproteins and ferritin; the metabolism of iron, copper, and bile pigments; and the detoxification of alcohol.⁶ Dynamic phase scanning with MRI contrast can provide a variety of diagnostic information about hepatocyte function, portal vein blood flow, and hepatic vein blood flow. Dynamic imaging of the hepatic artery and portal vein is performed 60 seconds after contrast injection, and the blood equilibrium phase occurs 120 seconds after contrast injection. Hepatocyte phase imaging, meanwhile, begins 20 minutes after contrast injection.

Although more conventional low–molecular-weight contrast agents can be used to achieve better visualization of the vascular structure or highly vascularized lesions, specific agents designed for hepatobiliary uptake have also been developed, including mangafodipir trisodium injection (Mn-DPDP), gadobenate dimeglumine (Gd-BOPTA), and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA). Mn-DPDP is a positive liver-specific agent that is preferentially taken up by hepatocytes and results in prolonged exposure, allowing for low doses of the agent to be administered. However, Mn-DPDP is not currently available in the United States. Adequate contrast can be achieved with doses as low as 10 mmol/kg body weight. Gd-BOPTA and Gd-EOB-DTPA are both positive gadolinium-based agents. Gd-EOB-DTPA is a liver-specific agent, whereas Gd-BOPTA can be used in liver studies as well as a variety of other diagnostic applications.¹

The Gd-BOPTA contrast agent is taken up by functioning hepatocytes and excreted into bile. It is possible to perform both dynamic postcontrast and delayed imaging studies of the liver with Gd-BOPTA studies. Dynamic imaging includes both hepatic arterial and portal venous phases of hepatic enhancement. The value of delayed imaging is to be able to distinguish lesions from functioning hepatocytes. Metastatic lesions and primary hepatic malignant tumors do not enhance or show uptake, and hepatic adenomas remain hypointense. A newer gadolinium-based contrast agent (GBCA), gadoxetate disodium, is a paramagnetic agent used in T1-weighted MRI studies of the liver in patients with known or suspected focal liver disease, and was approved by the FDA in October 2008. Recommended dosing of gadoxetate disodium is 0.1 mL/kg body weight (0.025 mmol/kg body weight), which is administered undiluted as a single IV bolus injection at a rate of 2 mL/second.⁷ Similar to other GBCAs, caution should be exercised when administering gadoxetate disodium due to the risk of nephrogenic systemic fibrosis (NSF), particularly in patients with known kidney disease.^7,8

RES-Specific Agents
Several RES-specific agents have been developed, some of which have been found to be useful in liver imaging applications. These agents are colloidal compounds composed of iron oxide core with a polysaccharide cover. After IV administration, the iron oxide particles are rapidly cleared from the plasma by the RES—approximately 80% through the liver and 12% through the spleen. These RES-specific contrast agents shorten T1 and T2. One available RES-specific agent, ferumoxides, is recommended for administration at doses of 0.05 mL/kg body weight diluted in 100 mL of 5% dextrose solution, administered by IV over a period of 30 minutes at a rate of 2 to 4 mL/minute. Imaging can be performed up to 3.5 hours after the end of this infusion process. The agent is safe and helps depict additional hepatic lesions on T2-weighted sequences. However, the use of this liver-specific contrast agent is not always practical due to the prolonged infusion time associated with administration.⁹

Lymph Node-Specific Agents
Reticuloendothelial system-specific contrast media agents that target the lymph nodes have also been investigated, including ultrasmall superparamagnetic iron oxide particles (USPIO), but are only commercially available in Europe at this time. Imaging is performed 24 hours after IV administration of the agent. Normal or benign lymph nodes take up the USPIO agent, and malignant lymph nodes do not take up the USPIO. Lymph nodes that accumulate the contrast will appear dark on T2-weighted images. Currently, there are no lymph node-specific agents approved for use in the United States. However, one USPIO lymph node-specific contrast agent, ferumoxtran-10, is currently under FDA review.¹⁰ Meanwhile, gadofluorines are another class of contrast agents that are currently under development to target normal and reactive lymph nodes. These agents cause abnormal nodes to appear bright on T1-weighted images.¹¹

Blood Pool Contrast Agents
Blood pool contrast agents exhibit a potential advantage over standard MRI contrast agents in that they remain in the blood for a longer period of time. The half-life of a blood pool contrast agent is 200 minutes. Depending on the size and composition of the product, blood pool contrast agents are cleared slowly by the kidneys or the RES. The primary purpose of blood pool contrast agents is to improve the efficacy of contrast-enhanced magnetic resonance angiography (MRA) images. In December 2008, the first imaging agent for MRA, MS-325 (gadofosveset trisodium) was approved by the FDA. Gadofosveset trisodium is a blood pool contrast agent that consists of gadopentetate and a protein-binding moiety that binds transiently to albumin after IV injection. The primary use of this contrast agent is to image blood vessels, and it is approved for the evaluation of aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease. AIOD occurs when iliac arteries become narrowed or blocked and may prevent the sufficient transport of oxygen and/or blood throughout the body.¹² Blood pool contrast agents provide a much larger window during which vascular images can be obtained as compared to gadolinium chelates agents. These contrast agents may ultimately prove useful in a variety of diagnostic applications, including coronary artery imaging, perfusion imaging, and peripheral vascular imaging.

Oral MRI Contrast Agents for Gastrointestinal Imaging
Several orally administered MRI contrast agents have been developed for use in gastrointestinal imaging. Perflubron was the first commercially available oral MRI contrast agent, and produces a signal void within the bowel lumen on T1- and T2-weighted images, therefore acting as a negative contrast agent. The agent moves rapidly through the gastrointestinal system, reaching the rectum within 30 to 40 minutes of administration, making the product inconvenient for widespread use.¹³ This limiting factor and high acquisition costs caused the product to be withdrawn shortly after approval. Another oral MRI contrast agent, manganese chloride tetrahydrate was approved by the FDA in 1997 and is primarily considered a T1-shortening agent. In studies with manganese chloride tetrahydrate administered as contrast, the intraluminal signal appears bright on T1-weighted images and dark on T2-weighted images. Although the product was approved by the FDA in 1997, it is not commercially available in the United States at this time.¹⁴ Ferumoxsil is the only oral MRI contrast agent currently marketed in the United States and is similar to ferumoxides, in that it is an iron particulate. The agent acts as a negative contrast agent and causes intraluminal signal loss on T1- and T2-weighted images.¹⁵

Clinical Applications: MRI Contrast in Studies of the Brain
Contrast enhancement is widely used in brain imaging. Gadolinium has proven invaluable in imaging the central nervous system because of the ability of this agent to pass through breakdowns in the blood-brain barrier (BBB). Extra-axial areas or areas outside the BBB will demonstrate normal enhancement. These areas include the falx, the petrous matrix, the choroid plexus, the pineal gland, and the infundibulum. Intra-axial lesions, such as infarcts, and tumors enhance on MRI due to a localized breakdown in the BBB. MRI modalities in brain imaging usually include sagittal T1-weighted sequences, axial T2-weighted sequences, T1-weighted and fluid-attenuated inversion recovery sequences, diffusion sequences followed by IV contrast T1-weighted sagittal sequences, and axial sequences. Sagittal T1-weighted and sagittal T2-weighted brain images are demonstrated in Figure 2.

In brain imaging, contrast is useful to evaluate the presence of a vascular supply if a lesion is found, to determine whether a BBB exists in association with the lesion, and to determine whether the contrast has leaked out of the vasculature into extracellular space. This feature helps to further categorize brain lesions. The lack of enhancement on imaging also offers valuable information. For example, high-grade gliomas generally tend to have greater BBB disruption and display greater contrast enhancement than low-grade gliomas. Active multiple sclerosis (MS) plaques also tend to demonstrate a greater BBB disruption and enhance more in comparison with older plaques. In this setting, the use of contrast can demonstrate which plaques are more acute. In many cases, metastatic brain disease can be demonstrated with the use of gadolinium. Studies have shown that at higher doses of gadolinium, metastatic lesions are more conspicuous. Patient management often changes according to the number of intracranial metastatic lesions demonstrated through contrast MRI.

Contrast MRI is also useful in stroke evaluation. In stroke, areas of infarct tend to enhance a few days after the initial event, and the enhancement generally lasts for several weeks. Contrast-enhanced MRA (CE-MRA) is an MRI modality used as a noninvasive alternative to other diagnostic studies in evaluating vascular disease related to stroke. CE-MRA studies are typically performed in the carotid and vertebral arteries to evaluate blood flow, stenosis, and obstruction, and to evaluate the extent of vascular disease in these vessels. Also, advances in software and gradient strength have allowed for shorter imaging times so that the actual passage of contrast in the arterial phase through the carotids and vertebral arteries can be captured.

Arteriovenous malformations (AVMs) can also be effectively imaged with contrast MRI. A normal MRI finding from a 3-dimensional (3D) time-of-flight study, compared with one demonstrating the presence of an AVM, is shown in Figure 3.

Clinical Applications: MRI Contrast in Studies of the Spine
With advances in MRI software and hardware, MRI has become the modality of choice for nearly all spine imaging. In fact, MRI of the spine is one of the most frequently requested MRI procedures. The demand for this examination is expected to increase with the advancing age of the patient population, resulting in an increasing prevalence of degenerative spine disease and lower back pain. However, imaging of the spine is sometimes challenging due to artifacts created by cerebrospinal fluid and vascular flow pulsation, respiratory motion, swallowing, and cardiac motion.

Lesions of the spine are classified by the region in which they occur, including those of the extradural space, intradural/extramedullary space, and the intramedullary space. The standard MRI examination of the spine usually consists of T1-weighted and T2-weighted sagittal sequences and a T2-weighted axial sequence. A PD sagittal sequence is also useful to help differentiate a disc bulge from an osteophyte. Sagittal short T1 inversion recovery (STIR) sequences are useful in evaluating vertebral body lesions, acute vertebral body fractures, ligamentous damage, and cord lesions.

The most common lesions of the extradural space are related to disc disease, degenerative changes, tumors, infection, and trauma. In young patients, discs appear hyperintense (bright) on T2-weighted sequences due to their water content. With increasing degenerative changes, discs become hypointense (dark) on T2-weighted sequences. Most extradural tumors, except for hemangiomas, can appear hypointense on T1-weighted sequences. On T2-weighted sequences, tumors can appear heterogeneous in signal intensity, or they can appear hyperintense. After the administration of contrast, homogenous enhancement is seen on T1-weighted sequences. In patients who have undergone a discectomy procedure, subtle enhancement is shown with MRI contrast and can differentiate between postsurgical scar tissue and a recurrent herniated disc. Scar tissue will show enhancement following the administration of IV contrast, whereas a recurrent herniated disc will not enhance (Figure 4). When planning an MRI contrast procedure in patients undergoing an evaluation of the extradural space, gadolinium contrast administration should always be used in patients with suspected infection and inflammatory disease. Bone lesions of the spine in particular can be well visualized with the use of gadolinium contrast.

The most common lesions occurring in the intradural/extramedullary space are neoplastic, infectious, inflammatory, cystic, or hemorrhagic in nature. Neoplasms present in this area can be either primary tumors or secondary metastases from another site. Primary spinal neoplasms include gliomas, specifically astrocytomas and ependymomas, which are the most common.

Lesions occurring in the intramedullary space specifically affect the spinal cord, and include those stemming from neoplastic, infectious and inflammatory, demyelinating, post radiation, vascular, neurodegenerative, and traumatic causes. In spinal cord hemangioblastomas, cyst formation can occur, most often superiorly and inferiorly to an enhancing central nodule after the administration of gadolinium contrast. Demyelinating disease or MS also frequently involves the spinal cord and results in visible lesions. These lesions are best visualized through PD and T2-weighted sequences. Acute MS lesions, less than a few weeks old, tend to enhance following the administration of contrast in MRI studies.

Vascular lesions of the spinal cord can be classified as either ischemic lesions or vascular malformations, both of which can be imaged with MRI contrast. Ischemic lesions of the spinal cord or cord infarctions are not common, and are associated with aortic disease arising from either an aortic dissection or aortic surgery. In ischemic lesions of the spinal cord, the flow of feeding vessels to the spinal cord is disrupted. This pathology appears as hyperintense on T2-weighted sequences. The most common areas affected by ischemic lesions of the spinal cord are the cervicothoracic region and the thoracolumbar regions. In these lesions, enhancement is evident following contrast administration.

Vascular malformations of the cord are classified as true AVMs, dural arteriovenous fistulas, and cavernous hemangiomas. These malformations can appear centrally hyperintense on both T1- and T2-weighted MRI contrast sequences.

Clinical Applications: MRI Contrast in Full Body Imaging
With advances in hardware and software, full-body MRI applications continue to expand. In the early days of MRI, body imaging was somewhat limited due to length of scan times and image quality. Improvements in software and hardware have reduced necessary acquisition times to 15 seconds or less with many MRI sequences, allowing for breath-holding techniques and better image quality.

Imaging of the Abdomen
Newer pulse sequences are capable of acquiring T1 and T2 sequences with shorter acquisition times, and fewer artifacts from respiratory, bowel, and vascular motion. T2-weighted sequences are useful for the detection and characterization of pathology and depiction of morphology. STIR sequences provide fat-suppression images, which is extremely important in imaging studies of the liver and pelvic organs. T1-weighted images are acquired using a variety of techniques, the most common being gradient-echo (GRE) sequences.

Opposed-phase imaging is a T1-weighted GRE method used to detect intracellular mixtures of fat and water. This sequence is useful in characterizing adrenal adenomas, depicting focal regions or fat in the liver, and characterizing some adnexal masses that occur near the uterus.

Gadolinium-enhanced T1-GRE imaging is commonly used in body imaging protocols. Multiple dynamic sets are acquired rapidly following a bolus administration of contrast. Hepatic arterial, portal, and delayed images can be obtained with these MRI contrast procedures. The series of images depict a pattern of enhancement that can be used to characterize lesions. This is especially important in the liver, prostate, and gynecologic pelvic organs to provide therapeutic or preoperative planning, as well as disease staging. In addition, dynamic enhancement and rapid imaging can be used to evaluate arterial flow in abdominal and pelvic vessels.

As previously discussed, hepatocyte-specific agents have been recently approved for MRI studies of the liver and show great promise. Oral contrast agents are also beneficial for abdominal imaging because they are a negative contrast for the gastrointestinal anatomy, thus allowing for improved visualization of abdominal organs.

Hemangiomas are very common, benign liver lesions. They are characterized by high (bright) signal on T2-weighted imaging. Procedures with gadolinium using dynamic and delayed imaging are helpful in characterizing these lesions.

Liver cysts are also benign lesions and can mimic neoplasms. These cysts demonstrate bright signal on T2-weighted sequences and are sharply circumscribed. Liver cysts will not enhance following IV gadolinium injection. Hepatic adenomas are another class of benign lesions, and appear heterogeneous on both enhanced and unenhanced imaging.

Hepatocellular carcinoma or hepatoma is a primary malignancy of the liver. The malignancies exhibit a moderately high T2 signal intensity and enhance rapidly following IV contrast administration.

Metastatic liver lesions caused by colon, breast, lung, or renal malignancies are also successfully imaged with MRI contrast. MRI of the liver is often performed in patients with cancer to detect and characterize metastatic lesions and differentiate between benign lesions and metastatic lesions stemming from the patient's primary cancer. Metastatic lesions can appear bright on T2 and dark on T1 sequences. A liver hemangioma imaged before and after the administration of contrast is shown in Figure 5. Following gadolinium injection dynamic T1 imaging with fat saturation, metastatic liver lesions may enhance very quickly in the arterial phase, or may demonstrate a ring of complete peripheral enhancement, followed by partial or complete fill on delayed views.

Renal cell carcinoma is the most common renal malignancy. These malignancies appear bright on T2 sequences and hypointense on T1 sequences. Enhancement occurs following the injection of gadolinium contrast. MRI is useful in staging renal cell carcinoma.

Pelvic Imaging
Magnetic resonance imaging studies of the prostate are used to evaluate tumor extension and differentiate between either extracapsular or direct seminal vesicle invasions. Although ultrasound is still considered the first-line imaging modality for evaluation of most benign disorders of the female pelvis, MRI studies are also used in this setting. Standard MRI protocols of the female pelvis consist of T1- and T2-weighted sequences of the pelvis in various planes, and dynamic imaging following IV gadolinium is helpful to better identify pathology. Figure 6 demonstrates enhanced imaging of pelvic fibroids after the administration of contrast in MRI.

Breast Imaging
Breast MRI was first approved in 1991 by the FDA as a supplemental tool to mammography to aid in the diagnosis of breast cancer, and is the second fastest growing MRI procedure in the United States.³ Breast MRI is primarily considered a problem-solving technology, especially in patients with very dense breasts, patients who have suspected lesions found on mammography or ultrasound, and patients with augmented breasts. MRI studies of the breast are highly sensitive to small abnormalities that can sometimes be missed with other breast imaging techniques. MRI can also help determine the type of surgery (lumpectomy or mastectomy) indicated when breast cancer is found. There are limitations with MRI because this modality cannot image breast calcifications, which are tiny calcium deposits that can indicate breast cancer.

In breast MRI studies, precontrast T1, T2, and STIR sequences are obtained of both breasts. The use of gadolinium contrast, followed by repeated dynamic T1 imaging with fat saturation, helps to characterize breast lesions. Lesions that tend to enhance rapidly and wash out rapidly following IV gadolinium are more likely to be malignant. The MRI modality often demonstrates multifocal lesions that are not always apparent on traditional mammography.

Cardiac Imaging
Cardiac MRI studies involve black-blood T1-weighted images as well as bright-blood T2-weighted cine techniques to evaluate cardiac function and morphology. Black-blood static sequences are used to evaluate cardiac anatomy and cardiac viability. Bright-blood cine sequences are used to evaluate cardiac wall motion and cardiac valves, and to assess ejection fraction. Contrast-enhanced MRI is particularly useful for obtaining high-resolution 3D MRA studies to evaluate the great vessels, cardiac perfusion imaging studies, and cardiac viability sequences.

Evidence of myocardial infarction (MI) has been shown to result in areas of enhancement following the injection of gadolinium contrast. Cardiac perfusion sequences are acquired dynamically for the evaluation of MI during rest and during physical or pharmacologic-induced stress, as well as delayed (15–20 minutes) T1 images of the myocardium.

Musculoskeletal Imaging
Contrast agents are not widely used in the musculoskeletal system, but gadolinium is useful to evaluate soft tissue tumors, distinguish between cysts and solid masses, and to differentiate between infection (inflammatory tissue) and abscess. The primary application of contrast in musculoskeletal imaging is intraarticular contrast used in MRI arthrography joint studies. These studies are performed by distending the joint and injecting diluted gadolinium directly into the joint. Intraarticular contrast is useful for evaluating the labrum in the shoulder and hip joints, torn triangular fibrocartilage complex ligaments in the wrist, and for the evaluation of repair of previously torn meniscus in the knee.

Important Safety Considerations with MRI Contrast
The need to administer an IV contrast agent in MRI studies requires important safety considerations. Patients undergoing MRI with contrast can potentially suffer from adverse reactions to GBCAs, and those who have experienced a reaction to another agent may also react to GBCAs. Particular caution should be used in administrating gadolinium agents to patients with a history of asthma or allergies, and in patients with a history of adverse reaction to a paramagnetic contrast media.

At standard doses, the side effects of gadolinium chelates are minimal when compared with those of iodinated contrast media, which can cause anaphylaxis and even death. Studies have shown that possible side effects associated with gadolinium contrast agents include a slight, transitory increase in bilirubin and blood iron; a 9.8% incidence of mild transitory headaches; a 4.1% incidence of nausea; and a 2% incidence of vomiting. Hypotension, gastrointestinal upset, and rash have all been reported at rates of less than 1%. The elimination of gadolinium occurs primarily through the kidneys, with approximately 80% excreted within 3 hours after administration, and 98% of gadolinium is recovered in 1 week.²

American College of Radiology Safety Guidelines
The American College of Radiology (ACR) recommends that those who have suffered from previous reactions can be treated with corticosteroids, and in some cases antihistamines, prior to the administration of the GBCA. Likewise, although the use of MRI is generally accepted as safe during pregnancy, the ACR recommends that studies with contrast agents should be avoided, if possible, during pregnancy.⁸

Although rare, cases of NSF have been reported in individuals with previous kidney disease who had undergone MRI studies with gadodiamide, a GBCA. As a result, the FDA recommends that clinicians should refrain from conducting imaging studies requiring the administration of GBCA in patients with advanced kidney disease, defined as those with a glomerular filtration rate (GFR) of less than 60 mL/min/m².¹ The ACR also recommends that patients with a history of renal disease, including solitary kidney, renal transplant, or renal tumor; aged older than 60 years; a history of hypertension; a history of diabetes; or a history of severe hepatic disease, liver transplant, or pending liver transplant, should receive an updated GFR assessment within 6 weeks of undergoing an imaging study requiring the administration of GBCA. Although these precautions should be strictly followed when administering GBCA, the contrast agents used in MRI studies are generally safe and do not pose excessive hazards to most patients.⁸

Conclusions
Advances in MRI hardware and software are resulting in expanded applications for diagnostic imaging with MRI. In addition, the introduction of specific contrast media for MRI have made noninvasive MRI studies more feasible, and continuing innovations in contrast agents could make MRI contrast studies possible in a wider range of diagnostic applications. Although safety is an important consideration when administering any contrast agent, those used in MRI are safe in many patients and increase diagnostic strength in many applications. With proper patient selection and planning, MRI contrast represents a fundamentally important diagnostic tool.

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