Stefan Kaminsky, Wolfram Clauss,
MD MD
#{149} Michael
Laniado, MD #{149} Marion Gogoll, MD #{149} Wolfgang Kornmesser, Langer, MD #{149} Claus Claussen, MD #{149} Roland Felix, MD
#{149} Mathias
Gadopentetate Agent: Safety
Dimeglumine and Efficacy’
To determine the safety and efficacy of gadopentetate dimeglumine as a bowel contrast agent, magnetic resonance (MR) imaging (0.5 T) was performed with a formulation of gadopentetate dimeglumine (1.0 mmol/L of gadopentetate dimeglumine, 15 gIL of mannitol, 6-17 mL/kg) in 133 patients with intraabdominal mass lesions. Mostly short-lived gastrointestinal side effects were noted in 32% of patients. Gadopentetate dimeglumine provided uniform hyperintense marking of the bowel and contrast enhancement in the region of interest in 81% of patients. Among 78 patients with images obtamed both before and after administration of contrast material, postcontrast improvement of lesion delineation was found in 62%. Among 55 patients with only postcontrast images, gadopentetate dimeglumine proved useful in 65%. Intravenous injection of scopolamine or glucagon effectively eliminated “ghost” images of the opacified bowel in 105 of 109 cases. The authors conclude that gadopentetate dimeglumine is a safe and effective bowel contrast agent for MR imaging. Index
terms: Abdomen, MR studies, 70.1214, 80.1214 #{149} Contrast media, effects #{149} Gadolinium #{149} Intestinal neoplasms, MR studies, 70.32, 70.1214 #{149} Intestines, MR studies, 70.1214 #{149} Kidney neoplasms, MR studies, 81.32, 81.1214 Lymphoma, MR studies, 80.34, 80.1214 #{149} Magnetic resonance (MR), contrast enhancement #{149} Pancreatitis, 77.291 #{149} Pelvis, neoplasms Radiology
1
From
1991;
the
of a reliable
bowel
of Radiology,
Klinikum
a Bowel
contrast
agent is one of the major drawbacks of abdominal magnetic resonance (MR) imaging (1). Various potential bowel contrast agents for MR imaging have been proposed, and some compounds are undergoing clinical
testing
in Europe
and
the
United States (2-10). These studies are being performed to identify a material with the combination of reliable bowel marking and low toxicity. Pneclinical and volunteer studies (phase I trials) at the Fneie Universitat Berlin suggested that a formulation of gadopentetate dimeglumine (Scheming AG, Berlin) with mannitol might be a safe and effective intraluminal agent for the gastrointestinal tract (8,9). The purpose of the clinical study in 136 patients reported here was to evaluate the safety and efficacy of this gadopentetate dimeglumine formulation as a bowel contrast agent in abdominal MR imaging. MATERIALS
AND
As part of a multicenter phase al of a gadopentetate dimeglumine mulation
for oral
fion,
131 patients,
dian,
59 years),
institution
mass lesions
and
rectal
aged were
Il/Ill
tn-
for-
18-88
years
recruited
(me-
at our
on the basis of abdominal identified with computed
to-
mography (CT). In five additional patients, there was strong clinical suspicion of an intraabdominal tumor, but CT findings were equivocal and there was no
proof
of a mass lesion.
inflammatory
nature
The tumorous of 89
Rudolf
Virchow,
Standort
lesions
or (65%)
or biopsy.
In
the five with
Chanlottenburg,
equivocal CT scans at initial presentation, the diagnosis was based on medical histo-
‘7, clinical symptoms, and the results of CT, including follow-up studies, or on a combination tients (15%),
of these methods. In 21 pano definitive diagnosis was made (Table 1). Three of the 136 patients could not be imaged because of technical restrictions, but they were included in the study of side effects after having ingested the contrast agent. Written informed consent to perform
MR imaging
with
ministration
of gadopentetate
Freie
Universit#{227}t Berlin, Berlin, Federal Republic of Germany (5K., MG., W.K., M. Langen, R.F.); Department of Diagnostic Radiology, Eberhard-Karls-Universit#{227}t Tubingen, Hoppe-Seyler-Stnasse 3, D-7400 T#{252}bingen, Federal Republic of Germany (M. Laniado, CC.); and Schering AG, Berlin (W.C.). From the 1988 RSNA scientific assembly. Received March 22, 1990; revision requested May 7; revision received September 18; accepted September 20. Supported by grant 01 VF 142 from the Bundesministerium f#{252}r Forschung und Technologie, Bonn, Federal Republic of Germany. Address reprint requests to M. Laniado. C RSNA, 1991
oral and/or
rectal
ad-
dimeglu-
mine was obtained from all patients after the nature of the procedures had been fully explained. Subjects under the age of 18 years and drastically ill or uncooperative patients were excluded from the study.
The
same
applied
to patients
scheduled for endoscopy, contrast material studies testinal tract, preoperative tion, and surgery within
conventional of the gastroinbowel prepara48 hours after
MR imaging. The contrast agent was provided in 100-mL vials as a clear, colorless, 10mmol/L aqueous solution of gadopentetate dimeglumine containing 15 g of The
gadopentetate
mine had been pH to 7.0 with
AG, Berlin).
administra-
e
Contrast
mannitol.
METHODS
was confirmed with surgery 26 patients (19%), including
178:503-508
Department
ACK
as
MD
prepared sodium
dimeglu-
by adjusting citrate (Schening
Immediately
before
the
use, 900
mL of tap water was added to form a 1.0mmol/L solution of gadopentetate dimeglumine with 15 g/L of mannitol. Referring physicians were instructed to allow patients to ingest only fluid for at least 6 hours before the examination. Seventy patients received a standard dose of 10 mL/kg of the 1.0-mmol/L solution. Fortytwo patients ingested less than 10 mL/kg due to their relatively poor condition. Eighteen patients underwent rectal administration mine
of gadopentetate
(70-360
mL),
dimeglu-
bringing
the
total
vol-
ume of contrast material mL/kg. As exceptions, ceived up to 17 mL/kg
to more than 10 six patients reof the 1.0-mmol/L
solution.
enemas
selection enemas involving
Five
received
factor for patients was a mass lesion the rectosigmoid
Abbreviations:
IV
only.
The
who received adjacent to or at CT. The
intravenous,
SE
=
spin
echo.
503
volume was determined by the patient’s ability to tolerate rectal administration without discomfort. The mode of administration varied according to the location of the tumor. If opacification of the stomach and proximal small bowel was required, the agent was
given immediately tient in the magnet agent was ingested
before (n
placing
the pa-
77). The
evenly
contrast
throughout
a
45-minute period small bowel was
if marking of the to be achieved (n
entire 23).
For opacification colon, an interval between ingestion
of the small bowel and of at least 60 minutes of gadopentetate di-
meglumine and MR imaging was allowed for passage of the solution through the intestine (n 36). In the first 48 patients and in 30 additional subjects (group 1), imaging was performed before and after administration of contrast material. Group 2 comprised 55 less cooperative and/or elderly patients. To reduce investigation time, only postcontrast scans were obtained in these cases. During the postcontrast examination, 106 patients received one to seven injections of scopolamine hydrobromide (Bus-
copan; Federal
Boehninger Republic
Ingelheim, of Germany)
evaluated
Ingelheim, diluted
inject
the
drug
from
The catheter long enough
outside
the
to
magnet.
Three patients received IV glucagon ly, Bad Homburg, Federal Republic
(Lilof
Germany) at a dose of 1-2 mg. In 34 cases, blood samples (10 mL) were taken imme-
diately before and 24 and 48 hours oral administration of gadopentetate
after di-
meglumine.
ana-
lyzed
Blood
for levels
and
serum
of creatinine,
were
aspartate
tate dimeglumine
aminotransferase, alanine aminotransferase, ‘y-glutamyl transpeptidase, bilirubin, and iron. Serologic analyses of gadopen-
tetate levels
dimeglumine, were not performed.
diagnostically the tumor
and mannitol
loops,
was
not
cally
useful).
about side effects. Patients were imaged
in the supine
best results
po-
Taste
verse
plane. Additionally, coronal images obtained in 47 patients and sagittal
were
msec and echo times obtained in the trans-
of
images were obtained in 30. A multisection gradient-echo sequence yielding
nine
to 20 contiguous
sections
used
(Table
were
2). Images
a 256 X 256 matrix
with
was also projected
two to eight
of section thickness. Three radiologists (S.K., M.L., W.K.) analyzed the MR images by visually inter-
504
them
Radiology
#{149}
in retrospect.
MR
images
dimegluto be diagnosti-
than
one imaging
was selected
a pathe
for data analysis.
Acceptance
The contrast agent was described as taste- and odorless by all 136 patients. In the 42 patients who ingested less than the standard dose of 10 mL/kg, volume and not taste was the limiting factor.
on
exci-
tations for each series. The section thickness varied between 7 and 10 mm, with 5mm sections used only in selected cases. Intersection gaps ranged from 0% to 50%
preting
If more
of
RESULTS
repetition
of 200-2,000 msec were
gadopentetate considered
half to
sequence was employed in imaging tient, only the pulse sequence with
sition with use of the body coil of a 0.5-T superconducting magnet (Siemens AG, Erlangen, Federal Republic of Germany). Multisection spin-echo (SE) images (sintimes 22-90
to be
useful; if less than margin was contiguous
mine
sion of MR imaging and blood sampling, patients
with
was considered
opacified
At the concluat the time of were questioned
gle- and double-echo)
image
quality (satisfactory or unsatisfactory [ie, no diagnostic images]) and (b) uniformity of the distribution of hypenintense contrast matenial in the region of interest (yes or no). In group 1 (n = 78), images were analyzed for pre- and postcontrast lesion delineation. Lesion margins were divided into thirds, and lesion delineation was scored according to whether one-third, twothirds, or all of the lesion was marked (“poor” = less than one-third of lesion margin delineated from adjacent structunes, “fair” = two-thirds of lesion margin delineated, and “good” all of lesion margin delineated). In group 2 (n = 55), the fraction of tumor margin contiguous to opacified bowel loops was estimated (if more than half of the tumor margin was contiguous to opacified loops, gadopente-
with saline (mean total dose, 50 mg). Injections were given through an intravenous (IV) tube that was placed in a cubital
vein before MR imaging. was connected to a tube
for (a) overall
comlorung. i nere was no correiation between the dose of scopolamine on glucagon and the occurrence of adverse reactions. None of the side effects required any therapy. No MR study had to be interrupted because of side effects. Median values of pre-
study
Owing to preoperative procedures, surgery, or discharge from the hospital, 13 patients could not be supervised over the entire 48-hour followup period. Thirty-nine (32%) of the remaining 123 patients who received
chemistry
No
results
in the
in whom blood samples were in the normal mange.
changes
in the
results
blood
tests
were
hours
after
administration
of the
recorded
24 and
48
of gado-
pentetate dimeglumine. In 30 of the 39 patients who experienced gastrointestinal side effects, the side patients
effects were had diarrhea
mild. (brief
Twenty episodes
with a maximum of two stools, accompanied by flatus in five patients), two had flatus, five had a feeling of “fullness,” two had nausea, and one had vomiting. One of the two patients
with
nausea
(who
received
13
mL/kg of gadopentetate dimeglumine) reported weakness and eyelid swelling for up to 48 hours after administration fortunately,
of contrast this patient
material. Uncould not be
reexamined because he was discharged from the hospital within hours
after
material
administration
and
mitted
by
five
had
small
abdominal
duodenum
bowel,
and
bowel
latter
patients,
subof the
minor complications disorders associated of bowel function. disease or pancreati-
the
cem with six
was Sixteen
large
compressing
24
of contrast
information
telephone.
30 patients with had underlying with irregularities Five had Cnohn tis,
Safety
blood
34 patients were taken
six
had
masses
and colon
obstruction. one
can-
Of the received
an
enema in addition to orally administered contrast material and one meceived only rectally administered gadopentetate dimeglumine (360 mL). February
1991
men. both
Twenty patients the midabdomen
In four
patients,
phomas
and
were
found
five
patients,
were
had and
lesions in the pelvis.
disseminated lymph
lym-
node
in all three results
metastases
regions.
of MR
In
imaging
normal.
Uniform distribution of contrast material with bowel loop opacification in the region of interest was found in 104 (81%) of the 128 patients with pathologic findings at MR im-
aging with
(Fig 1) and in the five patients normal results. Lack of contrast
material
in the
noted
area
of the
in 24 patients
tumor
(19%).
was
In six pa-
tients, this was due to delayed passage of gadopentetate dimeglumine through the gut because of bowel obstruction or commencement of MR
imaging
too soon
tion of contrast sit of gadopentetate delayed imaging tients. Nonuniform
gadopentetate reason
lack
patients,
was
of opacification
of interest
eight
administra-
dimeglumine
for
region
after
material. Rapid trandimeglumine or occurred in four padistribution of
the
the in the
in two
patients.
lesions
had
In no
an-
atomic relation to the bowel, precluding the presence of opacified loops in the region of interest. In the years Figure
1.
Tl-weighted
image
(SE 400/22)
of 20-year-old man with Cnohn disease. Uniform opacification of the distal small bowel allows delineation of the thickened wall of the terminal ileum (arrows). More than half of the lesion is adjacent to opacified bowel loops (ie, gadopentetate dimeglumine is diagnostically useful). The lower signal intensity of gadopentetate dimeglumine in the terminal ileum is related to the dilutional effect of 400 mL of iodinated contrast material given by mouth for CT 6 hours before administration of gadopentetate dimeglumine.
In the
remaining
nine
patients
who experienced adverse reactions, diarrhea with or without flatus persisted oven a longer period. The frequency of stools was higher than two times in 48 hours. Eight of these nine patients had diseases associated with irregularities of bowel function. Two
of these
patients
had
atitis. Active Crohn diagnosis in another
ceived
iodinated
(2.5%
oral
contast
sodium/meglumine
zoate; (400
chronic disease patient.
Gastrognafin, mL)
before
for
medium amidotni-
Scheming
AG)
CT
6 hours
abdominal
gadopentetate
pancrewas the He me-
dimeglumine
was given at a dose of 800 mL (16 mL/kg). A female patient presented with diarrhea of 3 months duration due to an islet cell tumor of the pancreas. She also had frequent stools for 48 hours after administration of ga-
Volume
178
Number
#{149}
2
aiter
side
effects
a disorder with mia
ii proceaure. patient with proof gastrointestinal
remaining four of these 24 patients, image quality was unsatisfactory and
a iiirotn
The remaining longed episodes was
unlikely
the
only
subject
with
to be associated
bowel irregularities due to Conn syndrome).
(hypokale-
Efficacy Among the 133 MR studies, image quality was graded as satisfactory in 129. Four studies were unsatisfactory
because of significant facts on both pre- and images. Slight blurring
motion artipostcontnast of images due
to “ghost” images of the opacified bowel occurred, to some extent, in the majority of cases. However, in 105 of the 109 patients who received either scopolamine or glucagon, injection of hypotonic agents significantly reduced “ghosting.” In four patients who ingested doses of contrast agent in excess of 14 mL/kg, administration of scopolamine (28-80 mg) failed to sufficiently eliminate ghost images of hypemintense bowel loops, but image quality was still satisfactory in all four cases. Lesions were confined to the upper abdomen in 77 patients and to the midabdomen in one patient; another 12 patients had pelvic tumors. Fourteen patients had tumors in both the upper abdomen and the midabdo-
bowel
loop
liably The
evaluated. results
marking
could
of lesion
group
1 were
as follows:
not
be me-
delineation
in
On
precon-
trast images, it was poor in 32 patients, fair in 30, and good in 16; on postcontmast images, it was poor in nine patients, fair in 16, and good in 53. Improvement of lesion delineation with use of gadopentetate dimeglumine was found in 48 (62%) of the 78 patients with pre- and postcontrast scans (Figs 2, 3). In 30 patients (38%), lesion delineation was not improved. Lack of improvement was due to good lesion delineation on precontrast images (n 16) or lack of contrast material in the region of interest (n = 7). (Also, four patients had no lesions, while in three, image quality was unsatisfactory, pmecluding improvement of lesion delineation.) In none of these 30 patients did
image artifacts of the opacified bowel interfere with lesion delineation. In group 2, gadopentetate dimeglumine nostically patients
ages
(Fig
was considered to be diaguseful in 36 (65%) of the 55 with only postcontrast im-
4). It was
not
considered
to
be diagnostically useful in the memaining 19 patients (35%) because lesions shamed no borders with bowel loops (n = 4), gadopentetate dimeglu-
Radiology
505
#{149}
mine was not present in the region interest (n 8), or lesions could be
well delineated el opacification patient image tory, and one
independent (n
of
of bow-
5); in another
quality patient
was unsatisfachad no lesion.
DISCUSSION Safety and most important gastrointestinal
efficacy are the two features of potential contrast agents for
MR imaging.
Our
strate
that
the
dopentetate has
an
results
oral
of ga-
dimeglumine acceptable
formulation
differs
The
is safe
and
The
oral
tolerance.
pound in that mate as a buffer nitol.
demon-
formulation
from
the
IV com-
it contains sodium citand 15 g/L of man-
capacity
of the
buffer
is
sufficient to neutralize 200 to 300 mL of gastric fluid of pH 1.0. The standard volume of 10 mL/kg of the 1.0-mmol/L formulation of gadopentetate dimeglumine administemed by mouth corresponds to onetenth L/kg
of the versus
volunteer
IV dose (ie, 0.01 0.1 mmol/L/kg)
studies,
fecal
was
measured
gadolinium
of inductively
coupled
spectrometry;
99.2%
temed
dose
within
was
5 days
cate that pentetate urn may rnucosa.
ride
of
emission adminis-
stools
data
mdi-
were to occur, 1% of the gadoabsorbed (ie,
is unlikely toxic reactions. of magnitude
median lethal dose cation measured The
to The less
of the in rats
of gadolinium organs
chlo-
adversely
af-
fected by gadolinium cations are the liver, spleen, and skeletal muscle (13). However, results of liver function both
tests remained unchanged healthy volunteers and
patients who (9). In a phase
underwent I trial
in the
34
blood
also
found
of gadopentetate
tients. trast
Uniform material
were
opacified
in 81% of our was
distribution present,
loops
pa-
of conand there
of bowel
in the
region of interest. To achieve this in routine abdominal MR imaging (ie, in patients in whom an abnormality
506
Radiology
#{149}
a. Figure
b. 3.
Postcontrast
improvement
of lesion delineation in 39-year-old woman with islet cell tumor of the pancreas (SE 400/22). (a) Precontrast image shows two areas of low signal intensity medial to the night lobe of the liver and ventral to the kidneys. The image does not allow prediction of whether these areas represent the bowel or mass lesions. (b) With use of intraluminal gadopentetate dimeglumine, one “lesion” is identified as the duodenum and there is opacification of the jejunal loops. The second low-intensity area was confirmed to be a mass lesion well delineated from the gastrointestinal tract (two-thirds of the lesion) and the netroperitoneal vessels (one-third of the lesion). Precontrast lesion delineation was graded as poor, whereas postcontnast delineation was graded as good.
tests
dimeglumine, use of mannitol was found to be mandatory for uniform distribution of contrast material in the entire small bowel and opacification of the ascending colon (9). This
was
2. Postcontrast improvement of lesion delineation on Ti-weighted images (SE 200/ 22) in 68-year-old woman with carcinoma of the cardioesophageal junction. (a) Precontrast image shows wall thickening at the level of the candioesophageal junction. The anterior and posterior gastric wall look normal. (b) After distention of the stomach with gadopentetate dimeglumine solution and IV injection of scopolamine, tumorous thickening of the anterior gastric wall is seen, indicating tumor involvement. In retrospect, the wall thickening at the candioesophageal junction shown on the pnecontnast image represented only approximately two-thirds of the lesion (fair delineation). Postcontrast lesion delineation was graded as good.
only traces of either gadodimeglumine or gadolinipass through the intestinal Even if intestinal decompo-
IV injection (12).
b.
Figure
means
from
These
MD MD
#{149} Michael
Laniado, MD #{149} Marion Gogoll, MD #{149} Wolfgang Kornmesser, Langer, MD #{149} Claus Claussen, MD #{149} Roland Felix, MD
#{149} Mathias
Gadopentetate Agent: Safety
Dimeglumine and Efficacy’
To determine the safety and efficacy of gadopentetate dimeglumine as a bowel contrast agent, magnetic resonance (MR) imaging (0.5 T) was performed with a formulation of gadopentetate dimeglumine (1.0 mmol/L of gadopentetate dimeglumine, 15 gIL of mannitol, 6-17 mL/kg) in 133 patients with intraabdominal mass lesions. Mostly short-lived gastrointestinal side effects were noted in 32% of patients. Gadopentetate dimeglumine provided uniform hyperintense marking of the bowel and contrast enhancement in the region of interest in 81% of patients. Among 78 patients with images obtamed both before and after administration of contrast material, postcontrast improvement of lesion delineation was found in 62%. Among 55 patients with only postcontrast images, gadopentetate dimeglumine proved useful in 65%. Intravenous injection of scopolamine or glucagon effectively eliminated “ghost” images of the opacified bowel in 105 of 109 cases. The authors conclude that gadopentetate dimeglumine is a safe and effective bowel contrast agent for MR imaging. Index
terms: Abdomen, MR studies, 70.1214, 80.1214 #{149} Contrast media, effects #{149} Gadolinium #{149} Intestinal neoplasms, MR studies, 70.32, 70.1214 #{149} Intestines, MR studies, 70.1214 #{149} Kidney neoplasms, MR studies, 81.32, 81.1214 Lymphoma, MR studies, 80.34, 80.1214 #{149} Magnetic resonance (MR), contrast enhancement #{149} Pancreatitis, 77.291 #{149} Pelvis, neoplasms Radiology
1
From
1991;
the
of a reliable
bowel
of Radiology,
Klinikum
a Bowel
contrast
agent is one of the major drawbacks of abdominal magnetic resonance (MR) imaging (1). Various potential bowel contrast agents for MR imaging have been proposed, and some compounds are undergoing clinical
testing
in Europe
and
the
United States (2-10). These studies are being performed to identify a material with the combination of reliable bowel marking and low toxicity. Pneclinical and volunteer studies (phase I trials) at the Fneie Universitat Berlin suggested that a formulation of gadopentetate dimeglumine (Scheming AG, Berlin) with mannitol might be a safe and effective intraluminal agent for the gastrointestinal tract (8,9). The purpose of the clinical study in 136 patients reported here was to evaluate the safety and efficacy of this gadopentetate dimeglumine formulation as a bowel contrast agent in abdominal MR imaging. MATERIALS
AND
As part of a multicenter phase al of a gadopentetate dimeglumine mulation
for oral
fion,
131 patients,
dian,
59 years),
institution
mass lesions
and
rectal
aged were
Il/Ill
tn-
for-
18-88
years
recruited
(me-
at our
on the basis of abdominal identified with computed
to-
mography (CT). In five additional patients, there was strong clinical suspicion of an intraabdominal tumor, but CT findings were equivocal and there was no
proof
of a mass lesion.
inflammatory
nature
The tumorous of 89
Rudolf
Virchow,
Standort
lesions
or (65%)
or biopsy.
In
the five with
Chanlottenburg,
equivocal CT scans at initial presentation, the diagnosis was based on medical histo-
‘7, clinical symptoms, and the results of CT, including follow-up studies, or on a combination tients (15%),
of these methods. In 21 pano definitive diagnosis was made (Table 1). Three of the 136 patients could not be imaged because of technical restrictions, but they were included in the study of side effects after having ingested the contrast agent. Written informed consent to perform
MR imaging
with
ministration
of gadopentetate
Freie
Universit#{227}t Berlin, Berlin, Federal Republic of Germany (5K., MG., W.K., M. Langen, R.F.); Department of Diagnostic Radiology, Eberhard-Karls-Universit#{227}t Tubingen, Hoppe-Seyler-Stnasse 3, D-7400 T#{252}bingen, Federal Republic of Germany (M. Laniado, CC.); and Schering AG, Berlin (W.C.). From the 1988 RSNA scientific assembly. Received March 22, 1990; revision requested May 7; revision received September 18; accepted September 20. Supported by grant 01 VF 142 from the Bundesministerium f#{252}r Forschung und Technologie, Bonn, Federal Republic of Germany. Address reprint requests to M. Laniado. C RSNA, 1991
oral and/or
rectal
ad-
dimeglu-
mine was obtained from all patients after the nature of the procedures had been fully explained. Subjects under the age of 18 years and drastically ill or uncooperative patients were excluded from the study.
The
same
applied
to patients
scheduled for endoscopy, contrast material studies testinal tract, preoperative tion, and surgery within
conventional of the gastroinbowel prepara48 hours after
MR imaging. The contrast agent was provided in 100-mL vials as a clear, colorless, 10mmol/L aqueous solution of gadopentetate dimeglumine containing 15 g of The
gadopentetate
mine had been pH to 7.0 with
AG, Berlin).
administra-
e
Contrast
mannitol.
METHODS
was confirmed with surgery 26 patients (19%), including
178:503-508
Department
ACK
as
MD
prepared sodium
dimeglu-
by adjusting citrate (Schening
Immediately
before
the
use, 900
mL of tap water was added to form a 1.0mmol/L solution of gadopentetate dimeglumine with 15 g/L of mannitol. Referring physicians were instructed to allow patients to ingest only fluid for at least 6 hours before the examination. Seventy patients received a standard dose of 10 mL/kg of the 1.0-mmol/L solution. Fortytwo patients ingested less than 10 mL/kg due to their relatively poor condition. Eighteen patients underwent rectal administration mine
of gadopentetate
(70-360
mL),
dimeglu-
bringing
the
total
vol-
ume of contrast material mL/kg. As exceptions, ceived up to 17 mL/kg
to more than 10 six patients reof the 1.0-mmol/L
solution.
enemas
selection enemas involving
Five
received
factor for patients was a mass lesion the rectosigmoid
Abbreviations:
IV
only.
The
who received adjacent to or at CT. The
intravenous,
SE
=
spin
echo.
503
volume was determined by the patient’s ability to tolerate rectal administration without discomfort. The mode of administration varied according to the location of the tumor. If opacification of the stomach and proximal small bowel was required, the agent was
given immediately tient in the magnet agent was ingested
before (n
placing
the pa-
77). The
evenly
contrast
throughout
a
45-minute period small bowel was
if marking of the to be achieved (n
entire 23).
For opacification colon, an interval between ingestion
of the small bowel and of at least 60 minutes of gadopentetate di-
meglumine and MR imaging was allowed for passage of the solution through the intestine (n 36). In the first 48 patients and in 30 additional subjects (group 1), imaging was performed before and after administration of contrast material. Group 2 comprised 55 less cooperative and/or elderly patients. To reduce investigation time, only postcontrast scans were obtained in these cases. During the postcontrast examination, 106 patients received one to seven injections of scopolamine hydrobromide (Bus-
copan; Federal
Boehninger Republic
Ingelheim, of Germany)
evaluated
Ingelheim, diluted
inject
the
drug
from
The catheter long enough
outside
the
to
magnet.
Three patients received IV glucagon ly, Bad Homburg, Federal Republic
(Lilof
Germany) at a dose of 1-2 mg. In 34 cases, blood samples (10 mL) were taken imme-
diately before and 24 and 48 hours oral administration of gadopentetate
after di-
meglumine.
ana-
lyzed
Blood
for levels
and
serum
of creatinine,
were
aspartate
tate dimeglumine
aminotransferase, alanine aminotransferase, ‘y-glutamyl transpeptidase, bilirubin, and iron. Serologic analyses of gadopen-
tetate levels
dimeglumine, were not performed.
diagnostically the tumor
and mannitol
loops,
was
not
cally
useful).
about side effects. Patients were imaged
in the supine
best results
po-
Taste
verse
plane. Additionally, coronal images obtained in 47 patients and sagittal
were
msec and echo times obtained in the trans-
of
images were obtained in 30. A multisection gradient-echo sequence yielding
nine
to 20 contiguous
sections
used
(Table
were
2). Images
a 256 X 256 matrix
with
was also projected
two to eight
of section thickness. Three radiologists (S.K., M.L., W.K.) analyzed the MR images by visually inter-
504
them
Radiology
#{149}
in retrospect.
MR
images
dimegluto be diagnosti-
than
one imaging
was selected
a pathe
for data analysis.
Acceptance
The contrast agent was described as taste- and odorless by all 136 patients. In the 42 patients who ingested less than the standard dose of 10 mL/kg, volume and not taste was the limiting factor.
on
exci-
tations for each series. The section thickness varied between 7 and 10 mm, with 5mm sections used only in selected cases. Intersection gaps ranged from 0% to 50%
preting
If more
of
RESULTS
repetition
of 200-2,000 msec were
gadopentetate considered
half to
sequence was employed in imaging tient, only the pulse sequence with
sition with use of the body coil of a 0.5-T superconducting magnet (Siemens AG, Erlangen, Federal Republic of Germany). Multisection spin-echo (SE) images (sintimes 22-90
to be
useful; if less than margin was contiguous
mine
sion of MR imaging and blood sampling, patients
with
was considered
opacified
At the concluat the time of were questioned
gle- and double-echo)
image
quality (satisfactory or unsatisfactory [ie, no diagnostic images]) and (b) uniformity of the distribution of hypenintense contrast matenial in the region of interest (yes or no). In group 1 (n = 78), images were analyzed for pre- and postcontrast lesion delineation. Lesion margins were divided into thirds, and lesion delineation was scored according to whether one-third, twothirds, or all of the lesion was marked (“poor” = less than one-third of lesion margin delineated from adjacent structunes, “fair” = two-thirds of lesion margin delineated, and “good” all of lesion margin delineated). In group 2 (n = 55), the fraction of tumor margin contiguous to opacified bowel loops was estimated (if more than half of the tumor margin was contiguous to opacified loops, gadopente-
with saline (mean total dose, 50 mg). Injections were given through an intravenous (IV) tube that was placed in a cubital
vein before MR imaging. was connected to a tube
for (a) overall
comlorung. i nere was no correiation between the dose of scopolamine on glucagon and the occurrence of adverse reactions. None of the side effects required any therapy. No MR study had to be interrupted because of side effects. Median values of pre-
study
Owing to preoperative procedures, surgery, or discharge from the hospital, 13 patients could not be supervised over the entire 48-hour followup period. Thirty-nine (32%) of the remaining 123 patients who received
chemistry
No
results
in the
in whom blood samples were in the normal mange.
changes
in the
results
blood
tests
were
hours
after
administration
of the
recorded
24 and
48
of gado-
pentetate dimeglumine. In 30 of the 39 patients who experienced gastrointestinal side effects, the side patients
effects were had diarrhea
mild. (brief
Twenty episodes
with a maximum of two stools, accompanied by flatus in five patients), two had flatus, five had a feeling of “fullness,” two had nausea, and one had vomiting. One of the two patients
with
nausea
(who
received
13
mL/kg of gadopentetate dimeglumine) reported weakness and eyelid swelling for up to 48 hours after administration fortunately,
of contrast this patient
material. Uncould not be
reexamined because he was discharged from the hospital within hours
after
material
administration
and
mitted
by
five
had
small
abdominal
duodenum
bowel,
and
bowel
latter
patients,
subof the
minor complications disorders associated of bowel function. disease or pancreati-
the
cem with six
was Sixteen
large
compressing
24
of contrast
information
telephone.
30 patients with had underlying with irregularities Five had Cnohn tis,
Safety
blood
34 patients were taken
six
had
masses
and colon
obstruction. one
can-
Of the received
an
enema in addition to orally administered contrast material and one meceived only rectally administered gadopentetate dimeglumine (360 mL). February
1991
men. both
Twenty patients the midabdomen
In four
patients,
phomas
and
were
found
five
patients,
were
had and
lesions in the pelvis.
disseminated lymph
lym-
node
in all three results
metastases
regions.
of MR
In
imaging
normal.
Uniform distribution of contrast material with bowel loop opacification in the region of interest was found in 104 (81%) of the 128 patients with pathologic findings at MR im-
aging with
(Fig 1) and in the five patients normal results. Lack of contrast
material
in the
noted
area
of the
in 24 patients
tumor
(19%).
was
In six pa-
tients, this was due to delayed passage of gadopentetate dimeglumine through the gut because of bowel obstruction or commencement of MR
imaging
too soon
tion of contrast sit of gadopentetate delayed imaging tients. Nonuniform
gadopentetate reason
lack
patients,
was
of opacification
of interest
eight
administra-
dimeglumine
for
region
after
material. Rapid trandimeglumine or occurred in four padistribution of
the
the in the
in two
patients.
lesions
had
In no
an-
atomic relation to the bowel, precluding the presence of opacified loops in the region of interest. In the years Figure
1.
Tl-weighted
image
(SE 400/22)
of 20-year-old man with Cnohn disease. Uniform opacification of the distal small bowel allows delineation of the thickened wall of the terminal ileum (arrows). More than half of the lesion is adjacent to opacified bowel loops (ie, gadopentetate dimeglumine is diagnostically useful). The lower signal intensity of gadopentetate dimeglumine in the terminal ileum is related to the dilutional effect of 400 mL of iodinated contrast material given by mouth for CT 6 hours before administration of gadopentetate dimeglumine.
In the
remaining
nine
patients
who experienced adverse reactions, diarrhea with or without flatus persisted oven a longer period. The frequency of stools was higher than two times in 48 hours. Eight of these nine patients had diseases associated with irregularities of bowel function. Two
of these
patients
had
atitis. Active Crohn diagnosis in another
ceived
iodinated
(2.5%
oral
contast
sodium/meglumine
zoate; (400
chronic disease patient.
Gastrognafin, mL)
before
for
medium amidotni-
Scheming
AG)
CT
6 hours
abdominal
gadopentetate
pancrewas the He me-
dimeglumine
was given at a dose of 800 mL (16 mL/kg). A female patient presented with diarrhea of 3 months duration due to an islet cell tumor of the pancreas. She also had frequent stools for 48 hours after administration of ga-
Volume
178
Number
#{149}
2
aiter
side
effects
a disorder with mia
ii proceaure. patient with proof gastrointestinal
remaining four of these 24 patients, image quality was unsatisfactory and
a iiirotn
The remaining longed episodes was
unlikely
the
only
subject
with
to be associated
bowel irregularities due to Conn syndrome).
(hypokale-
Efficacy Among the 133 MR studies, image quality was graded as satisfactory in 129. Four studies were unsatisfactory
because of significant facts on both pre- and images. Slight blurring
motion artipostcontnast of images due
to “ghost” images of the opacified bowel occurred, to some extent, in the majority of cases. However, in 105 of the 109 patients who received either scopolamine or glucagon, injection of hypotonic agents significantly reduced “ghosting.” In four patients who ingested doses of contrast agent in excess of 14 mL/kg, administration of scopolamine (28-80 mg) failed to sufficiently eliminate ghost images of hypemintense bowel loops, but image quality was still satisfactory in all four cases. Lesions were confined to the upper abdomen in 77 patients and to the midabdomen in one patient; another 12 patients had pelvic tumors. Fourteen patients had tumors in both the upper abdomen and the midabdo-
bowel
loop
liably The
evaluated. results
marking
could
of lesion
group
1 were
as follows:
not
be me-
delineation
in
On
precon-
trast images, it was poor in 32 patients, fair in 30, and good in 16; on postcontmast images, it was poor in nine patients, fair in 16, and good in 53. Improvement of lesion delineation with use of gadopentetate dimeglumine was found in 48 (62%) of the 78 patients with pre- and postcontrast scans (Figs 2, 3). In 30 patients (38%), lesion delineation was not improved. Lack of improvement was due to good lesion delineation on precontrast images (n 16) or lack of contrast material in the region of interest (n = 7). (Also, four patients had no lesions, while in three, image quality was unsatisfactory, pmecluding improvement of lesion delineation.) In none of these 30 patients did
image artifacts of the opacified bowel interfere with lesion delineation. In group 2, gadopentetate dimeglumine nostically patients
ages
(Fig
was considered to be diaguseful in 36 (65%) of the 55 with only postcontrast im-
4). It was
not
considered
to
be diagnostically useful in the memaining 19 patients (35%) because lesions shamed no borders with bowel loops (n = 4), gadopentetate dimeglu-
Radiology
505
#{149}
mine was not present in the region interest (n 8), or lesions could be
well delineated el opacification patient image tory, and one
independent (n
of
of bow-
5); in another
quality patient
was unsatisfachad no lesion.
DISCUSSION Safety and most important gastrointestinal
efficacy are the two features of potential contrast agents for
MR imaging.
Our
strate
that
the
dopentetate has
an
results
oral
of ga-
dimeglumine acceptable
formulation
differs
The
is safe
and
The
oral
tolerance.
pound in that mate as a buffer nitol.
demon-
formulation
from
the
IV com-
it contains sodium citand 15 g/L of man-
capacity
of the
buffer
is
sufficient to neutralize 200 to 300 mL of gastric fluid of pH 1.0. The standard volume of 10 mL/kg of the 1.0-mmol/L formulation of gadopentetate dimeglumine administemed by mouth corresponds to onetenth L/kg
of the versus
volunteer
IV dose (ie, 0.01 0.1 mmol/L/kg)
studies,
fecal
was
measured
gadolinium
of inductively
coupled
spectrometry;
99.2%
temed
dose
within
was
5 days
cate that pentetate urn may rnucosa.
ride
of
emission adminis-
stools
data
mdi-
were to occur, 1% of the gadoabsorbed (ie,
is unlikely toxic reactions. of magnitude
median lethal dose cation measured The
to The less
of the in rats
of gadolinium organs
chlo-
adversely
af-
fected by gadolinium cations are the liver, spleen, and skeletal muscle (13). However, results of liver function both
tests remained unchanged healthy volunteers and
patients who (9). In a phase
underwent I trial
in the
34
blood
also
found
of gadopentetate
tients. trast
Uniform material
were
opacified
in 81% of our was
distribution present,
loops
pa-
of conand there
of bowel
in the
region of interest. To achieve this in routine abdominal MR imaging (ie, in patients in whom an abnormality
506
Radiology
#{149}
a. Figure
b. 3.
Postcontrast
improvement
of lesion delineation in 39-year-old woman with islet cell tumor of the pancreas (SE 400/22). (a) Precontrast image shows two areas of low signal intensity medial to the night lobe of the liver and ventral to the kidneys. The image does not allow prediction of whether these areas represent the bowel or mass lesions. (b) With use of intraluminal gadopentetate dimeglumine, one “lesion” is identified as the duodenum and there is opacification of the jejunal loops. The second low-intensity area was confirmed to be a mass lesion well delineated from the gastrointestinal tract (two-thirds of the lesion) and the netroperitoneal vessels (one-third of the lesion). Precontrast lesion delineation was graded as poor, whereas postcontnast delineation was graded as good.
tests
dimeglumine, use of mannitol was found to be mandatory for uniform distribution of contrast material in the entire small bowel and opacification of the ascending colon (9). This
was
2. Postcontrast improvement of lesion delineation on Ti-weighted images (SE 200/ 22) in 68-year-old woman with carcinoma of the cardioesophageal junction. (a) Precontrast image shows wall thickening at the level of the candioesophageal junction. The anterior and posterior gastric wall look normal. (b) After distention of the stomach with gadopentetate dimeglumine solution and IV injection of scopolamine, tumorous thickening of the anterior gastric wall is seen, indicating tumor involvement. In retrospect, the wall thickening at the candioesophageal junction shown on the pnecontnast image represented only approximately two-thirds of the lesion (fair delineation). Postcontrast lesion delineation was graded as good.
only traces of either gadodimeglumine or gadolinipass through the intestinal Even if intestinal decompo-
IV injection (12).
b.
Figure
means
from
These
