Date Published: August 3, 2017
Publisher: Public Library of Science
Author(s): Caroline Jung, Sabine Christiansen, Michael Gerhard Kaul, Eva Koziolek, Rudolph Reimer, Jörg Heeren, Gerhard Adam, Markus Heine, Harald Ittrich, Xianwu Cheng.
The aim of the study was to quantify atherosclerotic plaque burden by volumetric assessment and T1 relaxivity measurement at 7T MRI using Gadospin F (GDF) in comparison to en face based measurements.
9-weeks old ApoE-/- (n = 5 for each group) and wildtype mice (n = 5) were set on high fat diet (HFD). Progression group received MRI at 9, 13, 17 and 21 weeks after HFD initiation. Regression group was reswitched to chow diet (CD) after 13 weeks HFD and monitored with MRI for 12 weeks. MRI was performed before and two hours after iv injection of GDF (100 μmol/kg) at 7T (Clinscan, Bruker) acquiring a 3D inversion recovery gradient echo sequence and T1 Mapping using Saturation Recovery sequences. Subsequently, aortas were prepared for en face analysis using confocal microscopy. Total plaque volume (TPV) and T1 relaxivity were estimated using ImageJ (V. 1.44p, NIH, USA).
GDF-enhanced in vivo MRI is a powerful non-invasive imaging technique in mice allowing for reliable estimation of atherosclerotic plaque burden, monitoring of disease progression and regression in preclinical studies.
Atherosclerosis is the underlying cause of life-threatening cardiovascular events such as myocardial infarction and stroke and represents the leading cause of morbidity and mortality . Animal models have become increasingly important tools to address key mechanistic and therapeutic questions that cannot be answered from human studies . Therapies aimed at reducing the risk factors for developing atherosclerosis and/or directly reducing the size of the plaque are being actively pursued, creating the need for more robust methods to determine plaque alterations in preclinical models of atherosclerosis [3,4].
The study demonstrates, that GDF-enhanced in vivo MRI is a powerful non-invasive imaging technique allowing for reliable estimation of plaque burden, monitoring of disease progression and evaluation of therapy response in preclinical studies.