title: Gradient echo MRI characterization of development of atherosclerosis in the abdominal aorta in Watanabe Heritable Hyperlipidemic rabbits.
abstract: OBJECTIVE
  The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed.
  
  
  METHODS
  Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killed for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm.
  
  
  RESULTS
  The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of age (p < 0.001). There was a small increase in aortic wall thickness between 50 and 73 weeks of age, but this was not significant (p > 0.05). The corresponding differences in lumen cross-sectional areas at 20, 50, and 73 weeks of age were not significant. These results were consistent with in-house historical histology data on this strain of rabbits.
  
  
  CONCLUSIONS
  High-resolution gradient echo MRI can follow disease progression in the WHHL rabbit spontaneous atherosclerosis disease model.
authors.affiliation: AstraZeneca, 21XF, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. yi-xiang.wang@astrazeneca.com
authors.forename: Yi-Xiang J
authors.initials: YX
authors.lastname: Wang
authors.forename: Hideto
authors.initials: H
authors.lastname: Kuribayashi
authors.forename: Maria
authors.initials: M
authors.lastname: Wågberg
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Holmes
authors.forename: Jean J
authors.initials: JJ
authors.lastname: Tessier
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
mesh_terms: D000375:Aging; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D017352:Echo-Planar Imaging / Q000379:methods*; D005260:Female; D006949:Hyperlipidemias / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits