Vascular remodeling and plaque vulnerability in a rabbit model of atherosclerosis: comparison of delayed-enhancement MR imaging with an elastin-specific contrast agent and unenhanced black-blood MR imaging.
OBJECTIVE
To compare delayed-enhancement (DE) magnetic resonance (MR) imaging with an elastin-specific contrast agent and unenhanced black-blood (BB) MR imaging with regard to vessel wall delineation and assessment of vascular remodeling and to test the prospective value for predicting plaque disruption in a rabbit model of atherosclerosis.


METHODS
All procedures were approved by the animal ethics committee. Atherosclerosis was induced in 14 New Zealand White rabbits by means of a 1% cholesterol diet and endothelial denudation. Plaque disruption was triggered with Russell's viper venom and histamine. Animals with atherosclerosis were imaged before triggering to identify plaques and vascular remodeling and after triggering to identify thrombus. Plaques were classified as nondisrupted (stable) or disrupted (vulnerable). Control rabbits fed a regular diet were imaged twice. Unenhanced T1-weighted BB MR imaging, DE MR imaging with an elastin-specific contrast agent, and T1 mapping were used to assess vascular remodeling and calculate the plaque area and vessel wall relaxation rate (R1 = 1/T1). Elastin was quantified by using elastica-van Gieson stain. Group comparisons were analyzed with the Mann-Whitney or paired t test. Agreement between methods was performed with Bland-Altman analysis.


RESULTS
Unenhanced T1-weighted BB MR imaging and DE MR imaging showed that, compared with nondisrupted plaques, disrupted plaques had larger plaque area (T1-weighted BB MR imaging: 5.1 mm(2) vs 5.7 mm(2); DE MR imaging: 6.0 mm(2) vs 7.9 mm(2); P < .001) and vessel area (T1-weighted BB MR imaging: 11.8 mm(2) vs 14.3 mm(2); DE MR imaging: 10.8 mm(2) vs 13.9 mm(2); P < .001) and underwent positive remodeling. Assessment of positive remodeling with DE MR imaging enabled better prediction of plaque disruption compared to that with unenhanced T1-weighted BB imaging (sensitivity: 83.7% vs 58.1%). DE MR imaging showed a stronger agreement with histologic findings, whereas the vessel area was overestimated with unenhanced T1-weighted BB imaging.


CONCLUSIONS
Compared with unenhanced T1-weighted BB MR imaging, DE MR imaging with an elastin-specific contrast agent enables more accurate assessment of vascular remodeling in the prediction of vulnerable plaque.
From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., A.I., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.P., A.S., P.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, England; and Lantheus Medical Imaging, North Billerica, Mass (D.C.O., R.R.C., S.P.R.).
Alkystis
A
Phinikaridou
Marcelo E
ME
Andia
Andreas
A
Indermuehle
David C
DC
Onthank
Rick R
RR
Cesati
Alberto
A
Smith
Simon P
SP
Robinson
Prakash
P
Saha
René M
RM
Botnar
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003287:Contrast Media / Q000494:pharmacology*; D004195:Disease Models, Animal; D004549:Elastin; D007091:Image Processing, Computer-Assisted; D018810:Magnetic Resonance Angiography / Q000379:methods*; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011446:Prospective Studies; D011817:Rabbits
D002791:Cholesterol, Dietary; D003287:Contrast Media; D004549:Elastin