Applied Radiology

Lawrence N. Tanenbaum, MD Assistant Professor, Neuroscience, Seton Hall University, and Section Chief, Neuroradiology, MRI & CT at the New Jersey Neuroscience Institute, JFK Medical Center, Edison Imaging Associates, Edison, New Jersey

When the use of contrast media was first introduced into the clinical practice of magnetic resonance (MR) imaging, it was used exclusively for central nervous system (CNS) applications. Over time, its use was expanded to include spinal and head and neck imaging as well. With the recent advances in MR technology, particularly high-performance magnets and power injectors, more advanced applications have come into practice. These commonly used clinical applications--many of which are off-label indications--include perfusion imaging, contrast-augmented MR angiography (MRA), breast imaging, cardiac imaging, and a variety of body applications including liver, kidney, and pelvic imaging.

This presentation will provide a brief overview of several of these advanced clinical applications of MR contrast agents, with particular attention to the use of power injection.

Power Injection Issues

The use of power injection of contrast media for MR imaging brings additional concerns to the clinical setting. The most important consideration is that of restricted patient access. Typically during power injection, the patient is fairly deep in the bore. Although the magnets in today's MR units are not as long as they used to be, the patient is often some distance from the clinician as the agent is being rapidly injected. This distance, combined with the fact that extravasation may occur at a point distant from the injection site, makes patient monitoring a challenge. Use of a non-ionic contrast agent, which is generally less toxic to the tissue, may help reduce the adverse effects of extravasation. In general, a lower-viscosity agent will require lower pressures to achieve rapid injection rates and, consequently, may be better tolerated.

A second consideration with the use of power injection is the need for very high patient tolerance since many of these images will be first-pass studies, e.g., a study of the arterial phase in the liver or a first-pass study of contrast through the vascular tree. Any local adverse effect or intolerance by the patient will most likely ruin a first-pass study.

To address these clinical concerns, clinicians need to consider several agent-specific attributes when choosing a gadolinum-based contrast agent for rapid injection. Agents that are non-ionic and low osmolar will result in fewer negative inotropic changes. This is particularly important for cardiac patients. Low-viscosity agents require less pressure to inject and allow for the use of smaller gauge needles and catheters. Gadolinium-based contrast agents with a cyclic molecular structure also have greater stability and, therefore, less potential for the release of free gadolinium into the body. This can be a concern over time in patients subjected to repeated injections, however, the role of free gadolinium is beyond the scope of this presentation.

Perfusion Imaging Studies

In recent years, perfusion imaging has become an essential tool in the radiologic armamentarium. It is used in the characterization and surveillance of brain neoplasm, the diagnosis of stroke and ischemia, and has indications in neuropsychology and psychiatry, as well as cardiology.

Perfusion imaging requires a rapid bolus injection of contrast agent. At our institution, we typically use a power injection rate of 3 to 5 mL/sec for perfusion studies. Some institutions use injection rates as high as 10 mL/sec.

Oncology

Figure 1 illustrates a typical scenario in which perfusion imaging can be beneficial in the diagnosis of a patient with a treated brain neoplasm. In this case, MR images reveal high T2 signal, significant mass effect, and edema. A non-specific area of blood-brain barrier breakdown is also visible. Spectroscopy, which is often used in such circumstances, shows elevation of the choline peak. These findings are all suspicious for residual tumor. The critical question is, "Are these simply postoperative changes, signs of radiation necrosis, or is there residual viable tumor tissue present?"

Perfusion imaging can help answer that question. A pixel-by-pixel perfusion map of the negative susceptibility enhancement curve reveals a ring of increased capillary density corresponding to the area of blood-brain barrier breakdown. This is a very compelling sign; in a generally hypovascular field, this ring of increased capillary density is indicative of vital tissue. In this case, not only was radiation necrosis present, but perfusion imaging revealed clear evidence of associated viable residual tumor.

In addition, perfusion imaging is often superior to blood-brain barrier breakdown imaging for assessment of lesion extent, particularly in cases involving primary brain tumors. Such tumors can have a degree of intact blood-brain barrier and, consequently, the enhancement seen in traditional studies may underestimate the extent of such lesions.

Figure 2 illustrates the case of a patient with a high-grade glioma. A blood-brain barrier breakdown study performed with fat suppression reveals a relatively unimpressive area of blood-brain barrier breakdown. With perfusion imaging, however, the lesion is far more striking and extensive. This particular tumor is much more impressive in its density of vascularity than in its integrity.

Stroke and Ischemia

Perfusion imaging can be used to assess the volume of ischemic brain in patients who present with brain attack or acute stroke. Results of a first-pass imaging study can provide an assessment of relative cerebral volume and mean time to enhance, providing an estimation of how much of the brain tissue is ischemic.

With mild alterations in flow, abnormally prolonged transit time is typically seen. As the flow alterations become more severe, it may manifest on a cerebral blood volume study as an area of compensatory increase. In the most severe cases, often correlating with frank infarction, a decrease in cerebral blood volume is typically seen.

Figure 3 shows the initial presentation of a patient who had suffered an internal carotid artery occlusion and small stroke. The mean-time-to-enhance map shows prolonged transit to the middle and anterior cerebral artery territory with very low perfusion in the actual area of infarcted brain. Several days later, after ineffective intervention, there was significantly more extensive volume of infarcted brain tissue, closely approximating the initial volume judged to be at risk.

Neuropsychology

Perfusion imaging is also used in neuropsychology, particularly for the diagnosis of diseases that are occult to structural imaging interrogation. One such circumstance is the dementias; perfusion imaging can be used to differentiate between the types of dementia. Figure 4 shows an elderly patient who presented with altered mental status. In such cases, it is necessary to differentiate Alzheimer's disease from other possible causes such as normal pressure hydroencephalus and multiple infarction-type dementia. In dementias of the Alzheimer's type, both perfusion MR imaging and nuclear medicine SPECT imaging will manifest temporal-parietal lobe hypoperfusion. In this particular case, a distinct decrease in perfusion in the temporal and parietal regions is present, suggesting a diagnosis of Alzheimer's disease. Similar findings would be seen on a metabolic test such as positron emission tomography (PET).

Perfusion imaging is also used to augment findings in cases of traumatic brain injury. Figure 5 illustrates the case of a 30-year-old woman with a traumatic brain injury in whom neuropsychological testing suggests a frontal lobe cognitive deficit. MR imaging reveals subtle structural abnormalities, particularly, volume loss in the frontal lobes. Although these changes are subtle, they were not present on a similar study performed 2 years earlier. This is a definitive finding and provides good structural correlation with the clinical findings in this case. The results of functional imaging, either SPECT or contrast-enhanced perfusion MR imaging, however, reveal an absolutely striking alteration in perfusion to the frontal lobes (figure 6). The functional imaging findings support the subtle structural findings and confirm the clinical diagnosis.

Myocardial Perfusion Imaging

With the current technology, it is possible to image a first-pass perfusion study of the whole heart. This exam is typically performed under adenosine stress and followed with a second exam approximately 5 minutes later after rest. This study is performed using a standard dose of contrast agent, power injected at a rate of 5 mL/sec. Any patient intolerance, either locally or with nausea, will ruin the study. Figure 7 shows a uniform left ventricular blush on the resting exam and an ovoid area of near transmural perfusion deficit on the interior wall.

The extremely short half-life of the stress agent used in such studies (approximately 7 seconds) permits the entire exam to be completed in the clinical setting in approximately 30 minutes.

Delayed Hyperenhancement

Another important concept in contrast-enhanced MR imaging is that of delayed hyperenhancement.

In infarction, contrast agent passes through the injured myocardial cell membrane. Hyperenhancement results from the combined signal of enhanced intracellular and extracellular spaces (figure 8). To obtain hyperenhanced images, a T1 prepared fast gradient echo scan is performed 10 to 15 minutes after administration of 0.1 to 0.2 mmol/kg of contrast agent. The extent of transmural enhancement correlates negatively with the likelihood of improved contractility in a segment of dysfunctional heart. This technique has the potential to become the ultimate assessment of viability.

MRA and Other Applications

Contrast-enhanced MRA studies overcome many of the limitations of traditional flow-based MRA, particularly when studying challenging areas, such as the thoracic outlet and great vessel origins. Enhanced MRA at our site typically involves a 1.0 to 1.5 mL/sec power injection of from 0.05 to 0.2 mmol/kg gadoteridol.

Contrast-enhanced MRA is now routinely used for renal artery assessment as well. In fact, MRA and CT angiography are close to eliminating conventional angiography from the initial work-up of patients with aorto-iliac and runoff disease. Prior to the use of contrast enhancement, brain arteriovenous malformations (AVMs) were very difficult to visualize. Now, in a 24-second scan, using half-dose contrast, striking images of AVMs can be obtained with the arterial nidus and venous structures in phase (figure 9).

Body applications have benefited from the recent technological advances in MR imaging as well. Faster scan acquisition coupled with tight power-injected contrast boluses routinely provides arterial and venous phase hepatic imaging. Figure 10 shows a patient with a hemangioma demonstrating early peripheral nodular enhancement on the arterial and portal venous phases with considerable contrast filling in on the delayed phase study.

Enhanced breast imaging is becoming increasingly important in clinical practice. Used to characterize lesions, this may someday have a routine role in the staging of breast cancer.

Conclusion

In summary, power injection of contrast agents for MR imaging is being used in a wide array of clinical settings including oncology, stroke and ischemia, neuropsychology, myocardial perfusion imaging, and others.

Power injection requires high patient tolerance. In over 5 years of clinical experience at Edison Imaging Associates with power injection of contrast agents, mainly ProHance ^® (gadoteridol), we have had a very low reaction rate with virtually no interrupted or suboptimal studies.