MODERATOR

Lawrence R. Muroff , MD Clinical Professor of Radiology University of Florida, and University of South Florida Colleges of Medicine Tampa, Florida

 

PANEL PARTICIPANTS

Pablo Delgado , MD Director, Residency Programs Clinical Associate Professor University of Missouri, Kansas City St. Luke's Hospital Kansas City, Missouri

Steven DiPrima , MD Neurovascular Radiologist HealthSouth Doctor's Hospital Coral Gables, Florida

Steven B. Halls , MD, FRCPC Director, Department of Oncologic Imaging Cross Cancer Institute Edmonton, Alberta, Canada

Emanuel Kanal , MD Professor of Radiology Director of Clinical and Educational MR University of Pittsburgh Medical Center Pittsburgh, Pennsylvania

Gerald M. Pohost , MD Professor of Cardiovascular Medicine University of Alabama at Birmingham Birmingham, Alabama

Val M. Runge , MD Rosenbaum Professor of Diagnostic Radiology University of Kentucky Lexington, Kentucky

Lawrence N. Tanenbaum , MD Assistant Professor, Neuroscience Seton Hall University Section Chief--Neuroradiology, MRI & CT

New Jersey Neuroscience Institute J.F.K. Medical Center--Edison Imaging Associates Edison, New Jersey

 

Dr. Muroff: Dr. Kanal talked about the gadolinium-based contrast agents being similar in some ways and dissimilar in others. Do these factors affect how you look at the agents?

Dr. Delgado: Many of us are in situations where the contrast agents may not be selected by the radiologist per se but I think it's valuable to have the information as a radiologist to make the distinction. If you have the choice of what contrast agents to use, safety, which seems to be quite similar for all agents, is extremely important. As Dr. Kanal pointed out and Dr. Tanenbaum mentioned in his presentation, radiologists should be educated regarding things like injection rates and viscosity and osmolality.

Dr. Muroff: You bring out a point that some of us don't have the choice of contrast agents. We noted when we polled our the registrants at Educational Symposia, Inc., meetings 3 years ago that about 70% of physicians were able to designate their agents. Today, less than half of them can. What's the experience on the panel? Can all of you pick the agents you want to use?

Dr. Halls: My experience is similar to that of Dr. Delgado in that it is a purchasing manager who will choose a vendor. Unless you raise strong objections and make your voice heard--and you can only do that once or twice on a couple issues per year--you are going to get what they decide, usually based on price.

I think we all have a similar experience that when it comes time to evaluate the vendors, you'll get a box of free samples from each and you try them all out dutifully and, honestly, I don't think you notice any significant difference in the clinical context. That being said, there are some things that do sway you one way or the other, and I think that's been brought out in the presentations.

Dr. Muroff: Dr. DiPrima, how about you? How are things done in your place? Do you get to pick what you want to use?

Dr. DiPrima: I think that it is less and less common that the radiologist is solely able to choose their own contrast agent, but your voice is heard. If you argue and there is not a large price difference, you are often able to at least sway the decision. At my institution, we tend to use a lot of higher-dose administration, particularly on older patients with cancer, and so the osmolality is a powerful argument. Additionally, administrators don't want to be caught on the wrong side of a lawsuit any more than we do. So with some success we've been able to help guide the decisions, as long as there is not a large difference in cost. It's important to remember, however, that we don't buy just one contrast agent. Computed tomography (CT) considerations, iodinated contrast, and so forth also enter into the decision-making process.

Dr. Muroff: Do the rest of the panelists choose your own agents? Dr. Tanenbaum, do you pick what you use at your hospital?

Dr. Tanenbaum: We are fortunate to actually make the choice of contrast agent at our institution, although sometimes it's a bit of a negotiation, and price is always a consideration. I think there are a number of compelling reasons, especially with the advanced applications, to favor one agent over the other. At my institution, we are fortunate enough to have the ability to do that: to choose or force a change at the institutions with which we are affiliated.

Dr. Muroff: Dr. Pohost brought up the concern about extravasation and viscosity in terms of cardiovascular applications. You do a lot of power-injecting. Is this part of your decision-making process?

Dr. Tanenbaum: Frankly, the differentiating issues--ionicity and osmolality--are critical issues in most of the advanced applications. Aside from the times when we actually put a butterfly in and hand inject, a significant percentage of our contrast administrations are power injected at higher and higher rates. Cardiac cases are done at least 5 mL/sec. And you heard Dr. Pohost advocate warming the agent and going as fast as you can, limited only by the pressure. Localized pain will kill your study. So it's critically important that you minimize all those factors and, frankly, those are the critical considerations. That is why we are so comfortable with ProHance in this clinical setting.

Dr. Muroff: Dr. Runge, do you have any other considerations in selecting an agent?

Dr. Runge: I'd like to address the issue of extravasation. We recently did a mouse study looking at extravasation. We took the four gadolinium-based contrast agents approved in the United States and did a rather large animal study. It was a blinded study from two perspectives. The individual giving the animal the extravasated dose was blinded to the agent used and also, of course, the pathologist that graded the response was blinded to the agent used. In this study, to no surprise, when we looked at necrosis and the other histologic changes that occurred with the gadolinium chelates, (and of course we were looking at extravasation, not intravenous injection) the results were statistically significant. The amount of necrosis and other histological changes correlated closely with osmolality. So the high-osmolar agent, Magnevist, caused the greatest damage, including necrosis and other histologic changes. The two low-osmolar agents, ProHance and Omniscan, caused the least. The newest agent on the market, which is intermediate in osmolality, OptiMARK, caused an intermediate response. These three groups were statistically differentiable.

I think one of the things that many radiologists have not looked at very intensely is specifically what amount of damage is caused in extravasation with the gadolinium chelates. In this study, we used saline as a control and we did a comparison with one of the old ionic X-ray agents. It turns out that the response to Magnevist, in terms of extravasation and damage, was not statistically differentiable from the old ionic X-ray agent. The only reason I think that we haven't been exposed to this problem to a greater extent in the last 10 years is that only recently have we been giving large doses and using power injectors and high rates.

In this study, the reaction with ProHance was not statistically different from saline. But again, that is based on the osmolality of the agents. I think that also reflects another thing that is in the package insert. In many of the countries, including Japan, the United States, and some European countries, the Magnevist package insert states and adds precautions about extravasation due to cases of necrosis. In the U.S. package insert, it says that one has to be careful in regard to this adverse reaction. Every time you give an intravenous injection, you need to make sure you look at the site. In fact, the package insert for Magnevist actually now warns about things like limb amputation that might occur because of a terrible reaction with extravasation. Therefore, I think with the high doses that we're now giving and the use of power injectors, we need to be very careful. I would advocate that anyone in that instance be looking at the low-osmolar agents.

Dr. Muroff : Dr. DiPrima, what's the mix in your practice of MR? How does it shake out in terms of neurologic, body, and musculoskeletal imaging?

Dr. DiPrima: I think that our experience probably parallels most surveys I've seen in the literature. We do probably about 60% neuro-imaging, including spinal images. The rest is predominately musculoskeletal, with an increasing but small number of body applications, including specifically: breast, which does require contrast; liver, which requires contrast; and MRCP hydrography of the pancreas.

Dr. Muroff: When you say a small percentage of others including breast, how many breast patients are you imaging in a month, let's say?

Dr. DiPrima: I would estimate about 10 a month on average.

Dr. Muroff: And what is your overall percentage of MR contrast use in your practice, per se, is it in that 20% ballpark?

Dr. DiPrima: No, it's substantially higher. We have a high mix of oncology patients so we're sitting somewhere in the 50% to 55% range for contrast administration.

Dr. Kanal: I'd actually be interested in polling the panel to find that out as well. Everyone's quoting 20% to 30%, but we have not been able to get below 40%. I'm interested in hearing what might be the cause of that, and to see if that's actually representative of this panel as well.

Dr. Muroff: I can tell you that among the people we've polled, the difference seems to be neuro-imaging. I also think that entrepreneurial centers tend to use contrast slightly less than other sites. In addition, I think that we're going to see cardiovascular and peripheral vascular imaging increasing the percentage of contrast use. That's on the other side of things, but maybe we can start and take the whole panel.

Dr. Delgado: I'm doing mostly body imaging, so I'm not involved directly with the neurologic applications. On the body application side, I tend to use contrast frequently, but I think it's being used more and more particularly with some of the applications that Dr. Tanenbaum spoke about, peripheral vascular studies and cardiac MR.

Dr. Muroff: Dr. Tanenbaum, you were talking about the rate of use at your practice being 20%.

Dr. Tanenbaum: Contrast use at our practice is about 20%, and, frankly, that reflects a predominantly neurology bias. We are probably 70% to 75% neurology, head and spine. The 20% number reflects a strict criteria for the utilization of contrast that coincides with a traditional list of indications. We don't give contrast for headache, we don't give it for new-onset seizures, or for seizures, or just because we are very worried about a particular case. We use a strict list of indications, and that puts us at very low utilization. We use it rarely in the spine, for tumor, and for only 10% of postoperative cases. We perform a decent amount of body work, and with high-performance gradient systems, contrast became routine in circumstances where before it was never used. Of course we use contrast in the advanced applications, but our numbers are in the low end of the range because we use these agents under strict circumstances, and avoid use in the more "fuzzy" circumstances.

It was interesting that Dr. Muroff mentioned that entrepreneurial centers use contrast less. He probably means, euphemistically, centers that run without a radiologist on site. On the other hand, there are entrepreneurial centers that will use contrast almost 100% of the time in neurology areas because there is a CPT code directly assignable to the post-contrast study, so it tends to shift the utilization in those circumstances as well.

Dr. Muroff: That's an interesting point, the way you segmented the entrepreneurial centers, and I think that's very important. What are your views about having a physician on site for contrast and injection? Again, I can tell you in our polling, 75% or more of the people believe very strongly that there should be a physician on site. I know that there is a very small, but very vocal minority of people who believe that ought not to be the case. Dr. Kanal, why don't you kick off this part of the discussion?

Dr. Kanal: Let me start it out by saying that this is, as you mentioned, quite controversial. It seems to me that if we're going to be administering drugs, we will, of course, be responsible for the reactions, but I don't want to be on the record saying I believe there has to be a physician on site. It's really my opinion that if we're going to be administering these agents, then someone who is in a position professionally to be able to identify, recognize, stabilize, and appropriately respond to any emergent reaction or adverse events that might occur should be on site, trained appropriately, and be able to demonstrate and document that they followed the protocols that this site has set. If I have a physician assistant there, if I have a nurse practitioner there, if I have anyone who is adequately trained in monitoring for adverse events, has a minimum of training in basic life support and CPR, knows exactly what the policy is for contacting professional assistance should it be required, and having them available in a timely fashion, I think that would probably be sufficient. The exact definition of "a timely fashion" is going to be controversial.

From a financial point of view, it's a considerable burden to have a licensed MD or DO on site for every MR center in the country. On the other hand, financial considerations may not be the ones that will attract the jury's attentions, should there be, God forbid, a life-threatening reaction, or a severe adverse reaction that was not adequately handled in a timely fashion. So most sites are essentially taking a gamble. They're saying that they have trained personnel and if it's a severe life-threatening reaction, just have them dial 911. As long as the patient prospectively understands that his or her chances of having a severe reaction are extremely small, but if one occurs there is no one on site to cover it: if the patient agrees to that, then perhaps you have a relationship that can be documented prospectively as being reasonable and understood. If the patient is not aware that these drugs have a very small rate of life-threatening adverse events and there is no one there to handle it, I'm not quite sure what defense the site is going to be able to offer.

Dr. Muroff: One of the purposes of this conference is to talk about myth versus reality. We're talking about adverse events, and I think one of the things that comes up in discussion often is nausea, as one of the adverse events that people see with all MR contrast agents. I was wondering if some of the panel can talk about their experience with one agent versus another to see if there are any differences in either number or types of adverse events.

Dr. DiPrima: Anecdotally, the two agents I've used are Magnevist and, more recently, ProHance. With regard to nausea, for some reason, I don't think our incidence is as high as some of the studies that were quoted earlier in the discussion. I wonder sometimes if that's an issue of prepping the patient properly. We fully tell the patients that they will feel some warmth in their arm and probably some nausea. We also tell them that it is unlikely that they will vomit, and for whatever reason, we just don't see it that often.

Dr. Delgado: I would say that probably most of us rely heavily on our technologists who feed us this kind of information. They are the ones who have direct contact with the patients. We are very fortunate at our institution to have some wonderful technologists, and the information given to me is that there are very few incidences of small adverse reactions, those being hives usually and nausea to some degree. I think most of the physicians here feel pretty comfortable giving ProHance. At our institution we have used Magnevist, ProHance, and Omniscan. Our experience demonstrates there are no differences in severity and/or frequency of adverse events between any of the gadolinium chelates.

To the point that, if a physician is not on site, a simple phone call alerting a physician that contrast is being administered is sufficient, and the likelihood of anything happening is very, very small.

Dr. Tanenbaum: Since we're not in a clinical trial setting, we're really only aware of some of the reactions. I think the technologists, to a certain extent, are really only going to comment on the cases that are true vomiting or near emesis. Mild nausea is going to escape our notice, unless we go out of our way to question the patient. I think that is why we get the impression that, colloquially, the drug is like water; we don't see many adverse events.

I made sort of a flip comment that we've seen more reactions with hand injections than we have with power injections, but, frankly, that is a true statement. We've had maybe one or two reactions in thousands of power injections, yet I can recall cases in which I've gone in and hand injected somebody and seen reactions with all the agents we've used. So, I think it is a very, very small number of patients that will actually come to our notice as having acute adverse events, and that's why the numbers are so low, and why it seems even lower with power injectors.

Dr. Runge: I'd like to address that issue of power injection because I think that it is true for the low osmolar non-ionic agents. We noticed early on, when just Magnevist was available, that when we gave a bolus our nausea rate went way up. And so I would caution people in this day when we commonly use power injectors, that you need to go with a low osmolar agent.

Dr. Tanenbaum: Let me just say this for the record, that my experience with power injections is 100% with ProHance, so my comments reflect only that agent's use.

Dr. Kanal: I would like to add, if I may, I think your experience is very real, and I'd like to present another potential explanation. We have the same experience that you have; with power injectors we find less of a "reaction rate." I don't believe that this is real. I believe that when we hand injected, you're standing there, by definition, and the patient will say something more readily than when it's a remote power injector and there's no one in the room. You just pick up less reactions.

There are differences in levels of nausea. The ones that we find out about are the ones that we consider disruptive nausea. The physicians in these retrospective surveys, I think, will tend to pick up what we refer to as disruptive adverse events, or the adverse events that tend to come to your attention whether you like it or not. A lot of the patients, for all we know, are having nausea, and, if it was a small amount, until you do a prospective study and ask them, they just wait for it to pass and don't say anything about it. Therefore, it never gets reported to anyone as an adverse event if you are not disrupted from your typical studies.

Dr. Muroff: Dr. Pohost, in your cardiac patients you said you've used both Magnevist and ProHance. Have you noted any differences in nausea rates with those patients?

Dr. Pohost: I haven't noticed any difference between the two, but again we have noticed that when you deliver the agent to the patient by power injection, the rate seems to decrease. The problem with the perfusion studies is that nausea may be caused by the stress agent. We know that those two agents produce nausea in and of themselves to a much greater extent than contrast agents.

Dr. Tanenbaum: I would just like to comment that we actually do have someone standing by the patient when we power inject. It's not quite the same experience as injecting someone anticubitally with them sitting next to you out of the magnet. The magnet is generally chirping and the patient is in the machine and there's a lot of things going on, but we are standing by doing the best job we can to monitor the site. I'm not sure, however, how effective we are at monitoring for extravasation with the patient in the bore. We make a reasonable attempt to be there at the patient's side when we power inject.

Dr. Pohost: I just want to make a comment with regard to the cardiac patient. We require that a physician be there anytime we place a cardiac patient in the magnet, and that's for obvious reasons. So there is a physician there all the time. It's not a law but it's our own internal laboratory regulation. We have had some patients who have had pulmonary edema episodes: things that you wouldn't want to have happen without a physician around.

Dr. Halls: We have had a very good experience. We switched from Magnevist to ProHance in 1993, and since then we have done over 5,000 injections. Our technologists log every reaction in a log book and we recently ran through that log book and discovered our rate was 1.3% for reactions of some kind. That's lower than some of the numbers we've heard in the presentations. Of that, 80% were either nausea or vomiting, and smaller percentages were minor things like headache and unsteadiness.

Dr. Muroff: Do you sense there is a difference from one agent to another, or have you only had experience with ProHance? How does your experience relate from one agent to another?

Dr. Halls: I'm just going to stick to saying I think it was equivalent to what it was before we switched to ProHance. But in my mind, it illustrates that the very act of asking the patient if they're having a reaction or standing by them influences the outcome and our numbers reflect where we don't ask. We just make note of what the patients tell us and it's been a good experience.

Dr. Muroff: In the 1970s, Dr. Anthony Lalli published a landmark study on contrast media and adverse reactions. He suggested that it was possible to talk a patient into a serious contrast reaction. I really believe he is right. Depending on the type of questions you ask and the approach to the patients, you can have a significant impact on adverse event rates.

Dr. Kanal: Dr. Halls, looking at the data here today, you note a 1.3% reaction rate in your retrospective review. Since you did not question the patients, that means these are the reactions that were spontaneously reported to you. And then the 5,280 Magnevist patients we studied had a 1.3% adverse reaction rate. It's amazing that your study and ours were that identical, considering that neither of us knew the other one was doing it at different times.

Dr. Halls: Our patients are cancer patients, and a lot of them come back for repeat imaging, and if you don't pick up reactions the first time, the patient will often mention to the technologist the next time that they had a delayed onset of hives. This way we still pick up ones we would normally miss.

When the purchase choice comes up, when you've got two agents that are exactly the same price, it is very nice to be able to say, we have had 5 or 10 years of experience with this particular agent. Anecdotally, about 6 months ago, one of our technologists reported that we had four reactions in 1 month. We've never had that before; it was always one or two or three or zero. So we said bring the numbers. We put them in the computer, did a chi-squared test on it, and, of course, it wasn't statistically significant. Then I wagered to them that during the next month there would be less than four reactions. I guaranteed it, and, of course, it was less than four. It just proves that adverse events are random and several reactions in a short period of time are generally not significant.

Dr. Muroff : Dr. Pohost, talking about safety: your cardiac patients are a special subset of patients that have so many superimposed problems going on. You talked about your concerns with injections rates. What about your concerns--or do you have any concerns--about osmolality and osmotic load in these patients, one agent versus another?

Dr. Pohost: We have great concerns because the possibility of these heart failure patients that we're studying for perfusion may have episodes of pulmonary edema or heart failure; exacerbations of heart failure are a real potential threat. The same thing is true of the iodinated contrast agents. We've had a few patients develop pulmonary edema in the magnet and you have to treat them rapidly. So it is something that is realistic and something that should go through your mind when you are trying to decide between a high- or low-osmolar agent.

Dr. Muroff: Dr. Kanal talked about whether or not there is supervision available on-site. Are there any risk factors that alert you to the fact that a particular patient might be more or less prone to have a reaction?

Dr. Runge: This is a very good question and often is asked nationally at meetings. I think you have to be very careful. Patients with asthma have a higher susceptibility to having an adverse reaction, as do patients with allergies to multiple medications or multiple different substances. If you look at the package inserts in general, those two conditions are mentioned. The third type of patient with increased susceptibility is one that is often not well-appreciated in the United States: those with a previous reaction to an iodinated agent. Such a prior reaction does put you in a higher risk category. So asthma, multiple allergies, and a prior allergic reaction to iodinated contrast media are all concerns.

Dr. Kanal: If I may add to that also, the allergy to a prior iodinated contrast administration just about doubles your incidence to about 6%. But an allergy to a prior administration of a gadolinium agent increases to over 20% the potential to react to a future one. In fact, at UPMC, our standard of care and policy is that if anyone has had an allergic reaction to a prior MR contrast administration--and we've used them all now so it doesn't make a difference to which one--then, when they come back, they receive a different agent, not the one they initially received.

There are stories about patients who have had adverse reactions to Drug X, and every single time they got Drug X, there was a problem. Then we gave them Drug Y with no problems whatsoever and we stuck with Drug Y since then. You can plug in anything you want for X and Y, because they have had a problem with this one, not that one, or that one and not this one. And it is that way across the board.

Dr. Tanenbaum: I'd just like to ask a question. With MR contrast agents, when would you pretreat? What criteria would you use?

Dr. Muroff: Does anybody on the panel pre-treat patients? Let's start with that question. Do you pre-treat any of your gadolinium patients whom you are concerned may be predisposed to a reaction?

Dr. Kanal: The only pre-treatment we'll do is if someone comes in with a history of a previous severe reaction, and the severe reaction is not to iodine. We've had patients anaphylactoid to iodine that I have not pre-treated when I give them any of the gadolinium-based agents. However, if they have had a severe, potentially life-threatening reaction to a gadolinium-based agent, and, for whatever reason we feel it's still indicated to give them another such agent this time, we'll switch to a different one and we will pretreat. But I will make an observation. I don't know if this is universally reflective of the reality of MR care in this country, but we do have our patients monitored on a pulse oximeter. We monitor everyone who is at increased risk for a potential significant reaction, even if it's just due to an iodinated reaction in the past. We monitor all patients who have had previous allergies, a history of allergy
or allergic respiratory phenomena, asthma, or an iodinated reaction.

Dr. Muroff: Let's deal with other issues of myth versus reality. Are there patients who ought not to get gadolinium? Dr. Halls, in your practice are there patients to whom you avoid giving gadolinium?

Dr. Halls: The answer is no. We use it when it's called for and it would take a very severe set of circumstances to persuade us not to use it.

Dr. Muroff: Dr. Delgado?

Dr. Delgado: I agree with Dr. Halls. The only indication probably would be, as Dr. Kanal pointed out, a severe reaction to gadolinium. But with patients with decreased renal function and cardiac patients, we don't hesitate at all.

Dr. Muroff: You go to a meeting and the first question and the last is always what about patients with severe renal failure. How do you deal with those patient, Dr. DiPrima?

Dr. DiPrima: In general, we administer a normal dosage to such patients when indicated. Our philosophy is not to give contrast unless it is indicated. But once that decision has been made, even somebody who is in renal failure gets a standard 0.1 mmol/kg dosage. We don't decrease our dosage.

Dr. Runge: I'd like to just clarify one point. It has never been shown with intravenous injection of the approved doses of gadolinium chelates that there is any deleterious effect upon the kidney. The only concern in renal failure would be with ultimate excretion of the gadolinium chelate and the possible issue of free gadolinium. So, when we are injecting a gadolinium chelate, we are, of course, not causing any renal damage.

Dr. Kanal: It should also be pointed out that, as you brought up so nicely the concept of myth versus reality, the package inserts on all of these agents have sickle cell as an area that one should be aware of a potential problem. I hope that anyone who reads this article can contact me if they have any idea why that has made it into the package insert of these agents. All four of the companies have been directed to do so, to my knowledge, by the FDA. It is true that sickled-cells do orient relative to the magnetic fields. The forces with which they orient are exquisitely small, to the point where they are felt to be less than normal physiologic forces on these cells as they go through the normal capillary flow. Nevertheless, any potential "potentiation" by these contrast agents makes no sense to me whatsoever. There are time-varying concerns, and I have no idea why that it is in the package inserts. We have most definitely administered these agents to patients with sickle-cell traits, sickle-cell disease, and have used it diagnostically when we felt it was clinically indicated without hesitation.

Dr. Muroff: I'd like to go into another area: high-dose uses or altered doses. Perhaps we can even get into low dose as well. But in high dose, I'd like to deal with two different issues, the first being the central nervous system (CNS) indications and then the other being the off-label indications. First let's deal with CNS. What percentage of times do you use greater than 0.1 mmol/kg for CNS patients in your practice other than angiography perhaps?

Dr. Kanal: When we presented the data for our study, we looked at the dose for that study as well as for
that initial study. We found that in the two studies, approximately 5% of patients received non-standard dose. Of that 5% about 50% received a low dose and 50% a high dose. So I would guess that not counting MR angiographic procedures for the body, approximately 2.5% of our patients who received contrast got high dose.

Dr. DiPrima: I think our experience will be a little higher than Dr. Kanal's. We do a lot of imaging before radiosurgery, and metastatic disease has become the number one indication for radiosurgery these days. You know that the detection of additional enhancing lesions is important. So we've become pretty frequent users of high doses of contrast agents prior to radiosurgery; not so much in a primary brain neoplasm, but in the scenario of intracranial metastatic disease.

Dr. Halls: We've dabbled in high-dose usage, but I think the reason that we're not doing it as much anymore has to do with the fact that we just keep getting busier and busier. You have to interact with the technologist to make the decision to give more, and so much of our practice is driven by protocols now. Especially in neurologic imaging, we don't do it much anymore. The few times that we do give extra doses is when we're doing breast MRI and we're localizing and I'm afraid the scans will have a gadolinium washout.

Dr. Delgado: We use gadolinium for our hepatic studies, some of our pelvic studies, and enhancement studies of the uterus and pelvis. When speaking to Dr. Tanenbaum, I told him that we routinely use high dose--double or even triple initially, although that has come down to some degree. I'd like to hear his comment regarding the fact that he is able to do it on standard dose.

Dr. Muroff: How about contrast use for MRA?

Dr. Tanenbaum: My feelings on the appropriate dose for MR angiography are kind of symptomatic of my feelings any time we get a contrast agent dose recommendation handed down to us in clinical practice. The recommendations always come in at the highest dose and I immediately go to the lowest dose and then try and figure out if that will work as well. We figured out that with surface coils and small body parts as we see in the neurology area that 0.05 mmol/kg works very well, and that's our standard dose. Half dose is our routine dose for neuroangiography. For single-station body imaging, we've been using standard dose and, frankly, I think that less than standard dose would work as well, but we're at standard dose. For aortic or renal imaging, we use 0.1 mmol/kg and the results are spectacular. We using very high resolution now and results are excellent.

Dr. DiPrima: Can that be attributed to your instrument a little bit?

Dr. Tanenbaum: Technically yes. I'm talking about a high-performance magnet and as opposed to a system with which you want to keep the blood pool opacified longer, but first pass, first or second generation high-performance gradients. When we do a run-off and we want to chase the agent "down to the legs," we will go to double dose. Now, is that because I know that double dose is better than single dose? No, and, frankly, I have a lot of experience at single dose doing run-offs. How do I get that? Well we practice with our technologists. We train our technologists by chasing renal studies down to the ankles. So I know how good single-dose studies look. But because my patient is there for that purpose, I want to give it the best shot and therefore we're using double dose. I understand that many institutions are using triple dose. It's nice to know you have that safety profile that allows you to do that, but until I prove to myself that triple is genuinely different and better, we're staying at double. Frankly, there are some issues of venous opacification that may be better at double dose than they are at triple dose. That is our experience after 5 years of doing a decent volume of cases.

Dr. Kanal: I'd like to suggest that Dr. DiPrima's comment is right on the money. It is exquisitely dependent on the hardware and software capabilities of your imaging system. If your system can generate the images it requires for the spatial and temporal resolution that you're asking for during first pass of a single-dose study, then there is no additional benefit--none--of double dose. Again, let me say that if you have the caveat that you are able in the temporal resolution of the first pass of the volume given in single dose, then someone would need to explain what the potential benefit of increasing dose would be. As you increase dose, you're not changing the relaxivity of the agent. It's still the same as it had been before. So the impact on the blood is going to be the same. The changes are going to occur when you have a somewhat slower system and the study takes longer to do, so if you just waited for first pass in the space of 7 or 8 seconds, it's already bolusing through and now you're already getting the tail end of that bolus. It's spreading out. Your relaxivity is not as great. Your T1 times are starting to lengthen out. Now you need to give a double dose just to physically give you a bigger bolus to be imaging during passage of a longer bolus.

What the industry will be heading toward is equipment that is faster that can get better temporal resolution at the same time as getting the same or better spatial resolution. As we head in that direction, there will be much more of a drive for the pharmaceutical firms that are manufacturing these agents to provide new agents entirely--agents that have higher relaxivities, that'll allow us even more imaging. It is especially true for perfusion imaging today that we accept what they have given us. It's far from ideal. We would far prefer to have an agent today that would be an even higher R1 and especially R2 value than what is available today.

Dr. Muroff: What about the whole concept when we're dealing with myth versus reality of lower field strengths versus higher field strengths and the impact that field strength has on contrast. Dr. Kanal, can you sort the myth from the reality?

Dr. Kanal: I'm afraid this does have reality there. It depends on the application. For example, if we're talking about perfusion-weighted imaging, then these are essentially used as susceptibility agents. And at that point, the amount of signal lost that you'll see on the image at a given imaging sequence is very definitely going to be dependent upon the field strength. The higher the field strength, the more sensitive you will be to a first pass if you're doing susceptibility imaging. So, for perfusion imaging, I would recommend going to the higher field strengths, and by higher, as high as your system will allow you to go. A 3 Tesla would be a lot nicer than a 1.5, for example.

For some of the other sequences, the physics being what they are, the relaxivities are not constant. They change as you change field strength, and what ends up happening is that the T1 shortening is not the same at a 0.5 Tesla as it is at a 3.0 Tesla. But in reality, what we end up suffering with more than anything else is a signal-to-noise trade-off. So as we're going to higher field strength, the bottom line is we are going to see more signal-to-noise overall in the image, and therefore the contrast enhancement should be that much more evident.

Dr. Muroff: Earlier we talked about using lower than the 0.1 mmol/kg in selected patients and about pituitary microadenomas and acoustic schwan-omas. Are other people on the panel using less than 0.1 mmol/kg and, if so, are you using it for different or other than those two indications?

Dr. Halls: We use the standard dose.

Dr. Tanenbaum: We do indication-related dosing across the board, which means we agree with everything that's been said to this point. We do use half dose if we are following a known meningioma and it works very well. Even perfusion imaging with half dose with meningiomas can be very striking.

Dr. Muroff: But Dr. Tanenbaum, I know you work with both 1.5 tesla units and open units. Do you alter your dosing based on the field strength? Will you use less than 0.1 mmol/kg if you're in an open magnet setting?

Dr. Tanenbaum: I'm glad you asked that question, because I wanted to add something to what Dr. Kanal said about low field. We have no problem creating signal-to-noise at low field. It just takes longer and we do it usually at the cost of lower spatial resolution, although not markedly lower. We really do think you can see the difference in the relaxivity in the contrast agents at 0.2 mmol/kg when compared to what we're used to in most of our practice at 1.5 Tesla.

We do everything we can to maximize enhancement. We'll use the various forms of fat suppression that are now available. We'll use magnetization transfer contrast, or background suppression to maximize contrast. But all of that said, with those devices at our disposal, we don't use half dose contrast at low field. We stay at the standard dose and, for the traditional circumstances, we might go to a high dose. Pituitary imaging is one of those circumstances where you're dealing with a dynamic effect at high field so you don't want the lesion to enhance that much, so you want to use a half dose. At low field, it's more of a steady state exam, and, frankly, I don't know that you really get an enormous amount of benefit going to half dose. So it's full dose and up at low field and the full range at high field for us.

Dr. Muroff: You mentioned magnetization transfer, and I know again we talked about polling that has taken place over the last 3 years. We've asked our registrants about their use of magnetization transfer. Less than 50% are using magnetization transfer in conjunction with single dose or standard dose contrast. Do you use it routinely in your practice?

Dr. Tanenbaum: That's a complicated question to answer. We do use it selectively. Our rule-out metastatic disease surveys will have a single plane done with magnetization transfer. Suppressing the background does improve the conspicuity of your contrast enhancement. It's not a triple dose worth, but it is more than you would get without magnetization transfer. There are some caveats. People have reported punctate lesions, punctate bright spots on magnetization transfer scans, which have been referred to as pseudo-lesions in the literature, that you'll see in the pre-contrast scan. We double-check against that in theory by not using magnetization transfer for the alternate planes, although, in 13 years, I have never seen a "pseudo-lesion" that I couldn't document with a different technique on another plane.

At low field, however, it's a very nice device. I do a 3-D magnetization transfer, gradient echo as my sole post-contrast sequence and display that in 3-D and often oblique planes. That is a very nice way to maximize enhancement at low field and still keep your time efficiency in hand. If your degrading echo is not adequate for contrast enhancement, even on high field, add a magnetization transfer pulse and it's a very viable technique for detecting enhancement.

Dr. Muroff: Are any of the panel members using magnetization transfer with single-dose contrast on a routine basis, as opposed to not using magnetization transfer pulse with your contrast?

Dr. Halls: We use it as part of our brain metastases protocol. One of our three post-gadolinium sequences has magnetization transfer. I wouldn't use it on all three because you'll lose the gray matter/white matter differentiation, which is nice, but it's helpful to use it.

Dr. DiPrima: We use at least
one sequence routinely. When you administer contrast, your intent is to detect abnormal contrast enhancement. Anything I can do to increase my sensitivity, I'm going to go ahead and do. I don't think the time penalty is substantial at all. For one sequence, typically our axial sequence, it's just not an issue with time.

Dr. Kanal: I'd just like to point out that the potential benefit of magnetization transfer is applicable regardless of the dose that is applied. If you're doing half dose, standard dose, double, triple, it doesn't make a difference what dose you're applying; the background suppression is applicable across the board and it should serve to increase your conspicuity regardless of which dose you gave.

Dr. Muroff: Bill Bradley made an excellent point at the last meeting I heard him lecture. He said he doesn't use it because in a very competitive, private practice environment, the pictures are not as good with a magnetization transfer pulse, and, basically, no matter how smart we can be, we're ultimately judged by our pictures in a clinical, competitive setting. That is a very interesting argument and may delineate the differences between private practice and academics.

Dr. Tanenbaum: I would say that I agree with that. The pictures are ugly, the contrast is suppressed, and you lose a little signal-to-noise. You can, on rare occasion, make a lesion harder to see. But when sensitivity is the critical issue, and you know that's the critical issue, I can make a pretty coronal image with a T1 FLAIR sequence if I like. On the other hand, when I'm following up my neuro-oncology cases, and they really want to see the morphology and the contrast between normal and abnormal tissue, we don't use magnetization transfer or fast spin echo techniques, which have a lot of magnetization transfer. We'll use some kind of really spectacular-looking T1 FLAIR, and that's the marketing issue that clinical practices have to consider as well.

Dr. Muroff: Again, this is something that I see less in academic practices and far more in clinical practices, that is the need or the desire to market your images to your competitive groups of physicians so that they send patients to you. Are there any other differences between academics and community practice in terms of contrast use that we might consider?

Dr. Runge: I would say that, responding to what people have said in terms of their percentage of contrast use, our percentage is more than 50% and that probably reflects the fact that we're getting a fairly sick patient population in an academic center.

Dr. Muroff: Dr. Halls, you're our lone representative from Canada. Is there anything in terms of practice patterns or reimbursement issues that impact contrast use in Canada differently than the United States?

Dr. Halls: In the private practice setting, it's still fee-for-service and sort of government-funded and that has some minor influence on how you plan your examinations. It may influence, in some cases, whether you do a pre-contrast examination and then bring the patient back later, or do it all in one setting. In the contract-for-service setting where I work at a cancer hospital, there's no influence at all. You want to get the patient in and out as quickly as possible and do whatever you need to do and you don't worry about it. There are a few private practices that are purely private practice settings where the patient has to pay and government doesn't pay, but even then there is hardly any influence on the cost of the procedure, actually.

Dr. Muroff: Our time is drawing to an end. I just want to thank everybody for your participation. I think it's been a very productive and informative session, and I hope all of you enjoyed it as much as I enjoyed moderating and participating with you. Thank you.