TG:

Let me start by saying that all of the presentations discussed, of course, applications for patients who were sick or may have cancer, who may have poor venous access, etc. One question to the panelists is do you notice a difference in the use of the gadolinium agents, if you have problems in these patients, such as extravasation? Low-ionic contrast media is likely to create less of a problem with extravasation. What do you do if you have extravasation? We talked a lot about bolus injections, but we didn't talk about the problems with that. What kind of problems have you seen?

MP: Well, I've had a lot of experience with extravasation. That's partly because with CT, we had a very rigorous protocol of meticulously checking the IV: are you getting a good blood return only using large caliber IVs. But with MR, we have smaller volume, and we've been less rigorous about checking the function of the IV before doing the study. We even will accept IVs that might be in the hand or the wrist that may not be as reliable as an IV in a large antecubital fossa vein. So one of the things I've noticed is that if you have an ionic high-osmolality contrast agent, the patient will let you know immediately when there is extravasation. They may want to terminate the study at that point.

But the lower osmolality nonionic features make the agent much better tolerated in the event of accidental extravasation. I've had a number of cases where the image would be blank. When I'd examine the patient, I'd see a huge volume of contrast there that got extravasated, and the patient hadn't even noticed that extravasation was occurring. That makes it easy to talk the patient into just redoing the IV and repeating it.

HR: I think there is one particular instance in which we have to be very careful: that's when we are doing sedated or anesthetized patients, because whether the contrast is ionic or not, they won't notice the extravasation. So, for example, in babies who are asleep for the MRs, we are always very vigilant to make sure we get a good blood return before injecting. The other cautionary tale is to avoid things like PICT lines when you are injecting high doses at high rates, because they can actually come apart internally with high injection rates. So we like to have an intercath, not a butterfly. We want to make sure if we are injecting a central line, that it is of sufficient size to handle the volume.

TG: We routinely also inject PICT lines in some cases. There I think the low viscosity really helps because the problem at the PICT line appears to be at the coupling of the IV to the catheter and the hub. That's what can blow, if the viscosity is high, because of the pressures that are developed.

MP: I think the use of the central line is an area where hand injection should be considered over power injection, because a low viscosity agent with hand injection might be able to go through a PICT line or other central line, you might be able to obtain an adequate study. Whereas using the power injection through a central line may destroy it and create an even worse situation.

TG: Does anybody else have any experience related to the specific injection local extravasations?

DB: I think when using a nonionic agent, we're more comfortable because the patient might be more uncomfortable while they're in our MR suite. But certainly with CT, we know we've had patients who were asymptomatic from large volume injections with CT contrast agents, and these can occur later. So I do think we need to emphasize when these occur, to maintain good contact with the patient, phone numbers, symptomatic treatment, and surgical consultation if it's needed.

MP: I have a rule that 50 mL is a dividing line between more serious and less serious extravasation. Has anyone else heard of the 50 mL rule? If you extravasate more than 50 mL, you must have a surgical or plastic surgical evaluation, but extravasations less than 50 mL are more likely to resolve on their own.

LK: We do a lot of contrast injections, and we're very meticulous in our technique, in placing the catheter and checking it after we place it. Or if it has been in there for while, in a patient coming down from the ward, we meticulously check it again. But we've recently been going to a higher dose, higher rates of injection, and we are seeing more and more extravasation. I think it's a little bit of a comfort margin, in theory, that we are using nonionics. One, as Martin said, the patients are very asymptomatic. But I'm hoping that there's less tissue necrosis associated with nonionic agents, versus the ionic agents, although I don't know if there's enough data to support that.

TG: We've noticed the lack of any thrombophlebitis that we've ever been able to identify in thousands and thousands of injections. We use a nonionic agent, and we haven't done the comparison of ionic versus nonionic agents, but it's interesting that we just don't see thrombophlebitis. Has anybody seen that post-gadolinium?

MP: I have had a case of a patient who received an ionic gadolinium contrast injection; at the time of the examination there was just a little bit of perivenous erythema. But the patient subsequently came back to the emergency room with a full-blown thrombophlebitis, and was admitted to the hospital and heparinized. Then eventually made a complete recovery.

TG: So it reiterates what Dr. Bluemke was saying, that these patients really need to be followed carefully and treated accordingly.

Now, let's discuss one of the other features about giving a bolus. Some of us use bolus injection in particular applications, some don't. Do you think that the contrast agents today have adequate "bolus-ability"? Do we need agents that could be given at higher rates? Have we reached a maximum?

DR: I've been giving gadolinium at tremendous rates, intra-arterially, which is a very rapidly growing area within interventional radiology. Many interventional renal cases are now done solely with gadolinium; and that's our practice. We often inject these at rates in excess of 5 mL/sec, so in aortic injections we can go as high as 20. In these applications, I like to use a nonionic agent. I don't have data to support this, but I expect that it's better tolerated by the patients, and also that the viscosity issues would make for a lower pressure injection. We've been using a nonionic agent for several years now in arteriography with wonderful results.

TG: Currently, none of the agents are approved for the arterial injection, but what is your experience clinically?

DR: It's a judgment; it's off-label usage of the agent. The patient outcome has been superb, especially in view of the lack of nephrotoxicity of the agent, when you are dealing with a patient who has underlying renal insufficiency. This is an area that's growing rapidly within the IR community.

TG: Right, because of the lack of nephrotoxicity of the agents.

MP: How do you compensate for the relatively lower concentration of gadolinium molecules within the gadolinium contrast, compared with the higher concentration of iodine molecules in the iodine contrast?

DR: It's a weaker radiodensity; it's not as radiodense as iodine. However, modern fluoroscopy units coming out have specific kV settings dedicated for gadolinium. You can select those settings and get more optimal images that approach the quality of iodine. But it's not as good, but often good enough to do the procedure safely.

HR: But better for the patient.

TG: Related to other factors that influence the choice of bolus, the highest bolus rate that we saw in the presentations was Dr. Bluemke. You spoke about 5 or 6 mL/sec for myocardial perfusion imaging. Dr. Rowley, what are you using in the CNS?

HR: Typically 3 or 4 mL/sec. For babies we'll go down to 2 mL/sec. It hasn't been necessary to go to 5 or 6, at least for our applications.

TG: Do you think that there is any reason to go higher for intravenous injections? Probably not, I imagine.

DB: I guess there's probably not a lot of reason to think that we should go higher. I think we tend to use 5 as our maximum, both for our neuro and cardiac applications. The doses we've looked at more seriously in CT work, and most of the highest CT doses, other people have certainly used 8 and 10 mL. Most people believe that 5 mL seems to be as high as we could go and I think there's probably a lot of parallels to what we are doing in MR so far.

TG: But then there is an important factor on the lowest injection rate that you would use for these perfusion studies, because an injection rate slower than a certain rate will give a problem in the arterial input function. It's no longer just a bolus function. So what do you think is the lowest injection rate that you like to use for perfusion imaging? It may be different in children versus adults, so let's talk about adults.

DB: For most of our injections we try not to go below 2 mL/sec. But empirically, I think that if you are going to capture first-bolus processes, which may take 10 to 15 seconds for the transit of contrast, at most, that we feel that you really need to deliver the contrast in a short concise bolus and get it in there. But we do feel compromised when we are using that slow an injection rate.

NH: There's actually been interest in modeling the pharmacokinetics for transfer constance, just with the T1 dynamic techniques, that actually you might be better able to model the slower infusion. So even at 1 mL/sec rates, if you know in fact that it's a steady infusion, than you can model that a little better. You might have more accuracy when you compute your transfer constance later. So there's published data suggesting that infusions are better than bolus methods.

TG: In some situations, such as T1-weighted imaging.

NH: Exactly. In T1-weighted dynamic images, when you are trying to derive for transfer consistence and permeability for breast cancer.

TG: On the other hand, most of the data is on susceptibility T2* imaging, which really indicates a higher injection rate.

NH: Right, there is much more.

RS: Tom, while we are still on this topic, for the body we typically use 2 mL/sec, that probably translates in Martin's lexicon as a fast hand-injection rate. I think that's approximately correct. We used to do hand injections routinely, and it was important to get a good firm injection. Now going to machine power injection using a standard dose, 2 mL/sec, seems to be quite adequate. But I think it's also intriguing if we start talking about higher doses, and using higher doses to look for small lesions and characterizing smaller lesions better in the liver; I think it may be essential to go with faster injection rates. So if we are using double or triple doses, I think it would make a lot of sense to look at going to 5 mL/sec.

In fact, there is some literature comparing MR with standard and spiral CT; MR is routinely better. We found in our studies that, if you look in the same patients, MR sees more lesions in at least 50% of patients, and has an impact on patient management, probably in that range too, when we compare standard MR with the 2 mL injection rate, and standard CT with the 2 mL injection rate. But I think it has been shown that if you increase the injection rate with CT on spiral or multidetector CT to 5 mL/sec, your results are much better as far as lesion detection. I think that would be the exact parallel we'd expect with MR, and maybe that should be the first step in looking at improving detection in evaluating patients for surgery. That probably is the more logical first step before going to looking at a combination of CTA and CTAP, to really look at increasing the dose and increasing the injection rate.

MP: To parallel CT, it's interesting also from the point of view of the nature by which we calculate the dose, there is a tendency at our institution to give a standard volume to every patient for CT. But in MR, we have a tendency to adjust the volume according to the patient's weight. There's a difference of opinion, whether the rate should also be adjusted based on weight, which sometimes can be done by diluting the gadolinium or if it should be a standard volume that you use in everyone for a standard rate. So this brings up several questions. Should we be dosing based on weight? Or should we go with the CT model of giving everybody the standard same volume? Should we be adjusting our injection rate based on weight as well?

NH: The reason to adjust by weight in MR is to get reasonably sane blood concentration, so that you might give rise to the same amount of single intensity change for the same amount of material there. That is the rationale to adjust for body weight.

MP: Okay, but if you are going to inject patients outside of the scanner, and then put them in and get your image, then adjusting by weight means that you've given the same amount of contrast per gram of tissue. But if you are going to image during the dynamic evolution of the contrast passage through the tissues, the amount that you inject is not as important as the rate at which you inject. So to have a correct matching to the patient size, you would really need to adapt your rate of injection to the patient weight.

NH: That makes sense.

MP: Then also, if you don't adapt the rate but you have the same duration of scan, then what's going to happen is your bolus duration is going to be different from patient to patient. So how it matches up with your mapping of k-space can vary as well. So I think there is just an enormous complexity in the sort of features of these injections that remains to be further analyzed.

RS: Cardiac input is also very important in this setting.

TG: Right. If the arterial concentration is related to the injection rate divided by the cardiac output, people with different heart functioning have different performance.

Let's get back to the issue of what rate you chose, in the liver, for example. Richard, you were suggesting that maybe then we ought to look at higher injection rates. Dr. Kramer, you pointed out that as the MR technology changes, we are able to image faster and then may capture the image in a shorter period of time. So that allows you to increase the rate, and that may in fact improve the detectability of liver lesions, or it could improve the MRA, for example.

Let's talk a little bit about dose. Currently, the high-dose indications for contrast agents is evaluation of intracranial metastatic disease. Dr. Rowley, do you want to comment on the merit there?

HR: Well, I think in most cases, we are still using single dose for most brain tumors, including metastases. But the enhancement that you see depends on the tumor itself, the dose, the delay after the injection, and, of course, the specific sequence. Our approach has been that when it is going to make a clinical difference. For example, a patient who is found to have one or two metastases is a candidate for either curative surgery or targeted radiotherapy. So, we'll go ahead and give the triple dose at the time of their treatment planning scan, at all the radiotherapy, and all the surgeries being done with a 3D MR. That is, we are anticipating that some patients may end up being excluded as surgical candidates, because we may find additional metastatic disease.

Another approach would be to use, for example, magnetization transfer in combination with single or double dose to improve the conspicuity. But in our hands, the key features are really getting at that triple-dose study, a volumetric acquisition, so we are not going to lose lesions between slices in inner-slice gaps. To get good T1 weighting, I see a problem with a lot of people trying to get better coverage, and letting it creep up toward a proton density-
looking scan. At that point, you don't know what you are looking at. So our approach is really two-fold, the standard imaging and then, at the time of treatment planning, we'll go ahead and give the triple dose if it is indicated.

MP: Do you think it's better to know that you need a high-dose study to look for absolutely every metastasis? Is it better to do a staged injection; or is it better just to give the triple dose right from the start?

HR: Well, that's a great question, because, of course, some tumors will take up contrast over the several minutes after the injection. In our shop, we'll usually know if we are going after a triple dose anyway. It's our approach to just give triple dose and we'll perhaps get, for example, the routine T1 or a T2 FLAIR, and then follow that with the 3D SPGR or an NP-RAGE to capture both the time and the added features of the volumetric acquisition.

TG: Well, I think that that should conclude our panel discussion. I'd like to thank all of the panelists as well as our coordinator, Oliver Anderson, from Applied Radiology . I'd also like to thank Amersham Health for their unrestricted educational grant to Applied Radiology , to support this symposium. Once again, thanks to all the speakers.

 

Continuing Medical Education Instructions

This CME article consists of text and related images appearing in the articles contained in this supplement. You should read the articles and accompanying images, refer to the references, and complete the self-evaluation quiz available online at www.appliedradiology.com/CME in order to be awarded CME credits. There is no charge for participating in this program.

Estimated time for completion: Six hours

Date of release: September 2002

Expiration date: September 2003

Program: FGS-001

In compliance with the Essentials and Standards of the ACCME, the authors of the articles in this CME tutorial are required to disclose any significant financial or other relationships they may have with the manufacturer(s) of any commercial product(s) or provider(s) of any commercial service(s) discussed in this program.

Dr. Hylton and Dr. Low state that no such relationships exist. Dr. Bluemke discloses relationships with GE Medical Systems as a consultant; Bracco Diagnostics via research support; and Amersham Health and Berlex Imaging as a member of their speakers bureaus. Dr. Grist discloses relationships with Amersham Health as a consultant and through research support, GE Medical Systems through research support, and ISG-Medical Advances as a consultant. Dr. Prince discloses relationships with GE Medical Systems, Siemens, Bracco, MedRad, and Mallinckrodt through patent agreements; with Topspins, Inc. as a major stockholder; and with GE Medical Systems, Bracco, and AMI through research support. Dr. Rowley discloses relationships with Amersham Health and Abbott Laboratories as a consultant and with GE Medical Systems as a member of their speakers bureau. Dr. Semelka discloses relationships with Berlex Imaging and Amersham Health through their speakers bureaus.