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?
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.
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.
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.
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.
Does anybody else have any experience related to the specific
injection local extravasations?
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
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.
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.
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?
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.
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?
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.
Currently, none of the agents are approved for the arterial
injection, but what is your experience clinically?
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.
Right, because of the lack of nephrotoxicity of the agents.
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
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
But better for the patient.
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?
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
Do you think that there is any reason to go higher for intravenous
injections? Probably not, I imagine.
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.
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.
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.
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
In some situations, such as T1-weighted imaging.
Exactly. In T1-weighted dynamic images, when you are trying to
derive for transfer consistence and permeability for breast
On the other hand, most of the data is on susceptibility T2*
imaging, which really indicates a higher injection rate.
Right, there is much more.
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
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.
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?
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.
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
That makes sense.
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.
Cardiac input is also very important in this setting.
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
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
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
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.
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
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.
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
. I'd also like to thank Amersham Health for their unrestricted
educational grant to
, to support this symposium. Once again, thanks to all the
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Dr. Bluemke discloses relationships with GE Medical Systems as a
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