Gadolinium-Enhanced Magnetic Resonance Imaging of Atherosclerotic Plaques in Comparison with Histopathology: An In Vivo Study in Aorta of Rabbits

조직병리와 비교한 죽상경화반의 가돌리니움 조영증강 자기공명영상: 토끼 대동맥을 이용한 생체 실험

  • Choi, Byoung-Wook (Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Hur, Jin (Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Lee, Hye-Jeong (Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Kim, Young-Jin (Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Kim, Tae-Hoon (Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Choe, Kyu-Ok (Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine)
  • 최병욱 (연세대학교 의과대학 영상의학과, 방사선의과학연구소) ;
  • 허진 (연세대학교 의과대학 영상의학과, 방사선의과학연구소) ;
  • 이혜정 (연세대학교 의과대학 영상의학과, 방사선의과학연구소) ;
  • 김영진 (연세대학교 의과대학 영상의학과, 방사선의과학연구소) ;
  • 김태훈 (연세대학교 의과대학 영상의학과, 방사선의과학연구소) ;
  • 최규옥 (연세대학교 의과대학 영상의학과, 방사선의과학연구소)
  • Published : 2009.06.30

Abstract

Purpose : We sought to evaluate enhancement of plaque with gadolinium-based contrast agent by magnetic resonance imaging (MRI) in comparison with histopathology, namely lipid-rich and macrophage-rich components that were two representative characteristics of plaque vulnerability using atherosclerotic rabbit aorta in order to determine which histopathologic component is relevant to the enhancement. Materials and Methods : New Zealand white rabbit (n=4, weight 3.0 to 3.5 kg, all male) was used for animal model of atherosclerosis. Atherosclerotic aortic lesions were induced by high-cholesterol diet and double balloon injury. T1-weight axial images were acquired before and after gadolinium-based contrast agent using a 3-T MRI. MR images and the matched histopathological sections (n=35) were divided into 4 quadrants or 3 (n=130). Enhancement ratio (ER, ER=SIpost/SIpre) on MRI was calculated for each quadrant and compared with histopathology in regard to lipid-rich and macrophage-rich areas. Results : Lipid-rich quadrants were 72 and fibrous quadrants were 58. The number of quadrants which had macrophage-rich areas was 105 and that of quadrants which did not have macrophage-rich areas was 25. ER was significantly higher in lipid-rich quadrants than in fibrous quadrants (mean ER 2.25c$\pm$0.41 vs. 2.72$\pm$0.65, p=0.013). ER poorly correlated with macrophage-rich areas when lipid-component was controlled (correlation coefficient -0.203, p=0.236). Conclusion : Lipid-rich plaques showed stronger enhancement than fibrous plaques using a standard gadolinium-based extracellular contrast agent. Macrophage infiltration did not correlate with degree of enhancement. Further study is warranted that account for optimal time of imaging after contrast injection using various plaque models from early to advanced stages and all possible parameters associated with contrast enhancement.

목적: 죽상경화반 유발 토끼 대동맥에서 자기공명영상을 이용하여 가돌리니움 조영제에 대한 경화반의 조영증강에 어떤 특징이 있는지 알아보고, 경화반 취약성의 대표적인 두 특징인 조직병리학적인 지질풍부 성분과 대식세포 풍부 성분과 비교하여 조영증강이 어떤 조직 소견에서 기인하는지 평가하고자 하였다. 대상 및 방법: 뉴질랜드 흰토끼 (4마리, 무게 3.0 $\sim$ 3.5 kg, 수컷)를 죽상경화반 모델로 사용하였다. 고콜레스테롤식이와 이중 풍선 손상을 이용하여 대동맥 죽상경화반을 유발하였다. 3-T 자기공명영상을 사용하여 가돌리니움 조영제를 투여하기 전과 후에 T1-강조영상을 얻었다. 자기공명영상과 상응하는 조직병리절편 (n=35)을 4개나 3개의 구역으로 나누었다 (n=130). 자기공명영상에서의 조영증강비 (ER, ER=SIpost/SIpre)를 각 구역마다 계산하여 조직병리의 지질풍부영역과 대식세포 풍부 영역과 비교하였다. 결과: 지질풍부 구역은 72개였고 섬유성구역은 58개였다. 대식세포풍부영역을 포함한 구역은 105개였고 포함하지 않은 구역은 25개였다. 조영증강비는 섬유성구역보다 지질풍부구역에서 높았다 (평균 조영증강비 2.25 $\pm$ 0.41 vs. 2.72 $\pm$ 0.65, p=0.013). 조영증강비는 지질성분을 제어했을 때 대식세포풍부영역과 잘 비례하지 않았다 (correlation coefficient -0.203, p=0.236). 결론: 표준 가돌리니움 기반의 세포외 조영제를 사용하였을 때 지질풍부 경화반은 섬유성 경화반보다 강한 조영증강을 보였다. 대식세포 침윤은 조영증강 정도와 비례하지 않았다. 초기부터 진행된 병기의 다양한 경화반 모델을 사용하고 조영증강과 관련된 모든 가능한 인자를 사용하여 조영제 투여 후 최적의 영상획득 시간을 결정하는 연구가 필요하다.

Keywords

References

  1. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006;47:C13-18. https://doi.org/10.1016/j.jacc.2005.10.065
  2. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995;92:657-671. https://doi.org/10.1161/01.CIR.92.3.657
  3. Carr S, Farb A, Pearce WH, Virmani R, Yao JS. Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. J Vasc Surg 1996;23:755-566. https://doi.org/10.1016/S0741-5214(96)70237-9
  4. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000;20:1262-1275. https://doi.org/10.1161/01.ATV.20.5.1262
  5. Yuan C, Kerwin WS, Marina S, et al. Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization. J Magn Reson Imaging 2002;15:52-67.
  6. Cai J, Hatsukami TS, Ferguson MS, et al. In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque; comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology. Circulation 2005;112:3437-3444. https://doi.org/10.1161/CIRCULATIONAHA.104.528174
  7. Kerwin WS, O'brien KD, Ferguson MS, Polissar N, Hatsukami TS, Yuan C. Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study. Radiology 2005;241:459-468. https://doi.org/10.1148/radiol.2412051336
  8. Kerwin W, Hooker A, Spilker M, et al. Quantitative magnetic resonance imaging analysis of neovesculature volume in carotid atherosclerotic plaque. Circulation 2003;107:851-856. https://doi.org/10.1161/01.CIR.0000048145.52309.31
  9. Calcagno C, Cornily JC, Hyafil F, et al. Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET. Arterioscler Thromb Vasc Biol 2008;28:1311-1317. https://doi.org/10.1161/ATVBAHA.108.166173
  10. Ibrahim T, Makowski MR, Jankauskas A, et al. Serial contrast-enhanced cardiac magnetic resonance imaging demonstrates regression of hyperenhancement within the coronary artery wall in patients after acute myocardial infarction. J Am Coll Cardiol Img 2009;2:580-588. https://doi.org/10.1016/j.jcmg.2008.12.029
  11. Lobbes MB, Miserus RJJHM, Heeneman S, et al. Atherosclerosis: contrast-enhanced MR imaging of vessel wall in rabbit model-comparison of gadofosveset and gadopentetate dimeglumine. Radiology 2009;250:682-691. https://doi.org/10.1148/radiol.2503080875
  12. Barkhausen J, Ebert W, Heyer C, Debatin JF, Weinmann HJ. Detection of atherosclerotic plaque with gadofluorine-enhanced magnetic resonance imaging. Circulation 2003;108:605-609. https://doi.org/10.1161/01.CIR.0000079099.36306.10
  13. Ohtsuki K, Hayase M, Akashi K, Kopiwoda S, Strauss HW. Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study. Circulation 2001;104:203-208. https://doi.org/10.1161/01.CIR.104.2.203
  14. Ogawa M Ishino S, Mukai T, et al. F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 2004;45:1245-1250.
  15. Wasserman BA, Smith WI, Trout HH III, Cannon RO III, Balaban RS, Arai AE. Carotid artery atherosclerosis: in vivo morphologic characterization with gadolinium-enhanced double-oblique MR imaging-initial results. Radiology 2002;223:566-573. https://doi.org/10.1148/radiol.2232010659
  16. Aoki S, Aoki K, Ohsawa S, Nakajima H, Kumagai H, Araki T. Dynamic MR imaging of the carotid wall. J Magn Reson Imaging. 1999;9:420-427. https://doi.org/10.1002/(SICI)1522-2586(199903)9:3<420::AID-JMRI9>3.0.CO;2-D