MR angiography of aortoiliac occlusive disease: a phase III study of the safety and effectiveness of the blood-pool contrast agent MS-325.
OBJECTIVE
To evaluate prospectively the safety and effectiveness of aortoiliac magnetic resonance (MR) angiography enhanced with MS-325 (gadofosveset trisodium) at a dose of 0.03 mmol/kg; effectiveness was defined as accuracy relative to the reference standard, conventional angiography.


METHODS
Study was approved by institutional review boards of participating institutions, and required national approvals were obtained. Study protocol conformed to Good Clinical Practice guidelines, and informed patient consent was obtained. Patients with known or suspected peripheral vascular disease received 0.03 mmol/kg MS-325 for aortoiliac MR angiography. They were also examined with conventional angiography. MS-325-enhanced MR was evaluated for safety and effectiveness. Along with unenhanced two-dimensional time-of-flight MR angiography, it was compared with conventional angiography for presence of vascular stenosis. Student t tests were used to identify significant improvement in diagnostic sensitivity, specificity, and accuracy, as well as quantitative characterization of stenoses by three blinded readers. Correlations between readers of conventional angiograms were calculated and compared with MR results.


RESULTS
In 174 patients, MS-325-enhanced MR angiography showed significant improvement (P < or = .001) in sensitivity, specificity, and accuracy for diagnosis of clinically significant (> or =50%) stenosis, compared with unenhanced MR. For all readers, areas under the receiver operating characteristic curve for both quantitative and qualitative measures of significant disease increased (P < .001) for MS-325-enhanced MR compared with time-of-flight MR. All readers also expressed higher confidence in diagnosis (P < .001) and found fewer images uninterpretable with MS-325 enhancement. All measures of interpretation accuracy approached corresponding measures of correlation between readers of conventional angiograms. Incidence of severe and serious adverse events with MS-325 was low. No patients were withdrawn from study due to adverse events or abnormalities in laboratory results. There were no clinically important trends in findings at hematology, blood chemistry, urinalysis, electrocardiography, or physical examination.


CONCLUSIONS
MR angiography with MS-325 provides significant improvement in effectiveness over unenhanced MR (and minimal and transient side effects) at a dose of 0.03 mmol/kg and was safe and effective for MR evaluation of patients with aortoiliac occlusive disease.
Goyen
Mathias
M
Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. mathias.goyen.de
Edelman
Mark
M
Perreault
Pierre
P
O'Riordan
Elaine
E
Bertoni
Hernan
H
Taylor
James
J
Siragusa
Daniel
D
Sharafuddin
Melhem
M
Mohler
Emile R
ER
Breger
Robert
R
Yucel
E Kent
EK
Shamsi
Kohkan
K
Weisskoff
Robert M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D001018:Aortic Diseases / Q000175:diagnosis*; D001157:Arterial Occlusive Diseases / Q000175:diagnosis*; D003287:Contrast Media; D005260:Female; D005682:Gadolinium; D006801:Humans; D007083:Iliac Artery; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity
D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; C109932:gadofosveset trisodium