May 12, 2008
The risks associated with gadolinium-based contrast agents in renally compromised patients or in infants are driving a growing interest in contrast-free options for MRI exams. Companies that produce MRI technology are addressing the issue with a variety of techniques to produce high-quality MR exams without contrast. But this raises an important question: Can noncontrast MRI techniques provide the same imaging clarity? According to several leading MRI technology producers, the answer is yes.
Back to Basics
Shahid M. Hussain, MD, PhD, a professor and the chief of abdominal imaging at the University of Nebraska Medical Center, says MRI use was initially developed without contrast media. Since the introduction of contrast, MRI techniques have evolved to encompass many other areas of the body. However, Hussain says it is important to realize that MR imaging has the capability to visualize tissues and organs on T1- and T2-weighted images without using any intravenous contrast media. Examples of these applications include time-of-flight or phase-contrast MR angiography (MRA) and MR cholangiopancreatography. Also, oral contrast media are not required for abdominal MRI because the bowel loops can be easily distinguished from other organs based on the intrinsic tissue contrast differences.
“MR has long been the modality of minimal risk as a diagnostic tool that minimizes interventions, use of other agents, and certainly no radiation,” says Joseph V. Fritz, PhD, director of MR clinical science for Philips Medical Systems North America. He points out that MR started as a contrast-free technique that was later supplemented with contrast for certain applications.
“Given the speed and dynamics possible with contrast MR angiography, facilities have continued to use this method,” Fritz says. “However, the NSF [nephrogenic systemic fibrosis] scare has increased demand for fast versions of noncontrast methods for patients with renal compromise.”
Compared with CT, Hussain views the capabilities of MRI as a safer modality for the following reasons:
• No radiation is used.
• No contrast injection is needed.
• Noncontrast MRI is likely to produce better images compared with noncontrast CT because the anatomic structures and organs, including bones, vessels, and muscles, are easier to recognize.
And while contrast media use is important for some MRI applications, “You are not depending on contrast-enhanced MRI sequences only when you perform MRI; contrast-enhanced images are often a small but important part of a comprehensive MRI protocol containing multiple T1- and T2-weighted sequences,” Hussain says.
For example, Hussain says his facility usually performs approximately 10 sequences through the upper abdomen for liver imaging. Among these, one sequence is repeated several times after contrast injection; the remainder of the exam can be obtained without contrast.
“So between 60% and 80% of the information needed can be obtained without contrast. For comprehensive and more conclusive exams, we prefer to have contrast-enhanced sequences as an integral part of our MRI protocol,” Hussain adds.
In patients with severe renal dysfunction who are often on dialysis and have an increased risk for developing NSF, radiologists and physicians will first consider noncontrast imaging methods, according to Hussain. However, if they find that contrast is needed, a risk-benefit analysis is performed. And if the benefits of using contrast for a particular case outweigh the risks for developing NSF, then contrast is sometimes used.
John Hipple, product manager for MR with Toshiba America Medical Systems, reports that the company has been working with contrast-free technology for nearly 10 years. “It was developed to improve the patient experience, eliminating the need for an injection and medication,” he says.
Toshiba was pursuing noncontrast exams long before the contrast problems were reported. Hipple says customers have expressed a need for alternatives that enable MRIs to be performed on patients who can’t receive contrast agents.
According to Hipple, certain noncontrast techniques work better in providing small vessel detail. Specifically, Toshiba’s equipment utilizes three proprietary contrast-free imaging techniques that can successfully perform MRA—fresh blood imaging, contrast-free improved angiography, and Time Spatial Labeling Inversion Pulse (Time-SLIP).
With Toshiba’s Time-SLIP technique, Hipple says radiologists can see into the vessel up to four times better. “Any cases where there is very slow flow—for example, the lower extremities—produce a better image using noncontrast MRI because when using dye, it doesn’t disperse evenly—for example, between the diseased and healthy leg tissue—resulting in a less accurate scan than had it been done contrast free,” says Hipple.
While the actual scan may take somewhat longer without contrast, exam times may not. Hipple says workflow improvements occur in eliminating the need for preliminary preparations associated with contrast use. “You have to keep in mind that with scans involving use of a contrast agent, there is a lot more set-up time to do such things as prepare the patient, inject the dye, and so on,” he adds.
Contrast agents are still necessary for some imaging, such as diagnoses of certain brain tumors and postoperative back surgery. However, vascular techniques, which usually require a large amount of contrast, are prime for contrast-free imaging.
Philips Medical Systems is working to adapt the old noncontrast techniques to create fast versions of noncontrast MR scanning methods. “These techniques are based on principles known and used for many years but now repackaged together with high speed-up factors permitted by modern scanners equipped with parallel imaging,” says Fritz.
Philips’ version of this technology is known as SENSE (Sensitivity Encoding), which provides faster imaging with more applications. For example, when used in combination with cardiac triggering, flow changes throughout the cardiac cycle can be used to better differentiate blood vessels from background tissue or even to visualize the flow dynamics. Philips has labeled this approach Triggered Angiography—Non Contrast Enhanced, or TRANCE.
With the fast imaging capabilities of MR scanners, contrast-enhanced angiography can be performed dynamically, allowing for the visualization of flow patterns. Also, long runoff studies can be performed using MR instead of catheter-based digital subtraction angiography approaches.
“The speed of acquisition available on today’s MR systems not only makes for reasonable-length noncontrast angio but also shorter contrast angiography, therefore requiring the administration of less contrast agent,” adds Fritz.
Because there is great familiarity and efficiency with established methods, most centers have continued using contrast-enhanced and noncontrast MRA. Philips has developed exam sequences it calls ExamCards that can be downloaded from its Web site. The ExamCards contain all the sequences needed to perform a specific exam and can be downloaded directly to Philips’ MR scanners. “When desired, the new variations of noncontrast angio can be added simply. New ExamCards have been generated for body and runoff studies without contrast, for example, and are available via the Philips Web site to make it one-click simple for an operator to run the angiographic technique[s] best suited for a given patient study,” says Fritz.
Physicians can alternate between contrast and noncontrast imaging on the same machine, which Fritz says they are pleased to have the capability to do should the need arise.
Stuart Clarkson, Americas MR training manager with GE Healthcare, says that in addressing the concerns regarding gadolinium use and the risk of NSF, GE Healthcare has 10 pulse sequences that can perform noncontrast MRI depending on the part of the body being imaged and how fast the flow is in that particular area.
Beginning at the head, 3D time-of-flight technology is used for the circle of Willis, which has a fast flow and lends itself nicely to a 3D technique. “Fast flow in this stationary anatomy permits excellent time-of-flight imaging with submillimeter resolution,” Clarkson says.
Moving to the carotid arteries, a 2D time of flight is used, and as you move to the aorta, GE’s 2D FIESTA sequence provides a clear blood-to-myocardium contrast for gated cardiac imaging. “FIESTA can image a large area in a short time while the patient holds his breath,” says Clarkson. The slower flow vessels in the liver are more difficult, but the FIESTA sequence in 2D can obtain a contrast-free scan in roughly six to eight seconds, permitting easy breathhold scan times. Combined with a fat suppression pulse, this technique is excellent for the portal vein, he adds.
For imaging renal arteries, GE’s FIESTA sequence is a useful tool. “Additionally, fast phase contrast uses the property of acquired phase shifts of flowing protons to generate noncontrast MR angiographic images of the renal arteries,” says Clarkson.
For the long, straight vessels in the legs and pelvis, a gated 2D time-of-flight sequence can be used. These vessels are very pulsatile but the ability to synchronize the pulse sequence to the heartbeat reduces motion within the vessel.
“The more advanced user generally prefers contrast-enhanced MRA methods. But in patients who can’t have contrast, the FIESTA-based sequence [with a breathhold] works well and is very robust,” says Clarkson. Most exam patients tend to receive gadolinium for this study, but those who can’t receive a contrast medium are imaged using one of 10 pulse sequences capable of noncontrast MRA, he adds.
On the Horizon
Siemens is rolling out a technique that has the potential to become the gold standard for MR imaging of the head: arterial spin labeling (ASL), which is slated for release in the U.S. market this spring. Initially, the techniques used for determining cerebral blood flow were invasive and involved the use of a gadolinium-based contrast agent. The principles behind ASL are similar to those utilizing exogenous contrast agents; however, it is completely noninvasive and involves no radiation, injections, or contrast media, according to Josef Pfeuffer, PhD, MR applications and development with Siemens Medical Solutions.
ASL is an MR technique using the water in arterial blood as an endogenous contrast agent to evaluate perfusion noninvasively. Working in conjunction with researchers at the University of Pennsylvania, Siemens developed syngo ASL, which uses magnetic inversion to tag blood in the neck arteries and arterial blood flowing in the head, which causes effects similar to using contrast. ASL scans take slightly longer—two to four minutes. Pfeuffer says that by compensating with some creative engineering using multiple coils, the increased measurement times are less of an issue than the benefits gained.
“This technique improves workflow because when using contrast in MRI, you can usually only perform one study in 10 minutes, then wait a half-hour before proceeding to another study. Because you are not relying on contrast, with ASL you can use the technology to complete different procedures: perfusion studies, anatomical studies, and even functional MRI [fMRI], where you can actually watch the brain at work,” says Pfeuffer. However, he notes that fMRI is currently generally used in clinical and neuroscientific research.
There are several applications for ASL, with tumor and pediatric perfusion imaging being the primary ones. Other applications include stroke, epilepsy, and degenerative diseases such as dementia and Alzheimer’s disease. In the future, Siemens is looking to use ASL in additional areas of the body, including renal and lung perfusion, both of which are active research areas.
Also looking to the future, GE Healthcare is collaborating with the University of Wisconsin-Madison to develop new pulse sequences that will significantly reduce scan times. The vastly undersampled isotropic projection reconstruction imaging is projected to cut down imaging time dramatically. “For example, a previously unreasonable scan time of 50 to 60 minutes becomes four to five minutes for large-phase contrast scans,” says Clarkson.
Toshiba also continues to pursue and develop contrast-free technology for as many new techniques as are viable. “We are always looking at where to go next,” says Hipple.
“Currently, a lot of possibilities exist to perform MR in a safe manner. The risk of radiation is one of the things that is really underestimated when choosing CT over MR,” says Hussain. With increasing numbers of CT exams and the associated risk of ionizing radiation and harmful effects of iodinated CT contrast media which can cause contrast-induced nephropathy even in otherwise healthy patients, Hussain sees great benefits in choosing MR as a valuable diagnosis tool with and without contrast media use.
— Annie Macios is a freelance writer based in Doylestown, Pa.