title: Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging.
abstract: OBJECTIVE
  To evaluate possible mechanism for delayed hyperenhancement of scarred myocardium by investigating the relationship of contrast agent (CA) first pass and delayed enhancement patterns with histopathological changes.
  
  
  METHODS
  Eighteen pigs underwent 4 weeks ligation of 1 or 2 diagonal coronary arteries to induce chronic infarction. The hearts were then removed and perfused in a Langendorff apparatus. The hearts firstly experienced phosphorus 31 MR spectroscopy. The hearts in group I (n = 9) and II (n = 9) then received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (0.05 mmol/kg) and gadolinium-based macromolecular agent (P792, 15 µmol/kg), respectively. First pass T2* MRI was acquired using a gradient echo sequence. Delayed enhanced T1 MRI was acquired with an inversion recovery sequence. Masson's trichrome and anti- von Willebrand Factor (vWF) staining were performed for infarct characterization.
  
  
  RESULTS
  Wash-in of both kinds of CA caused the sharp and dramatic T2* signal decrease of scarred myocardium similar to that of normal myocardium. Myocardial blood flow and microvessel density were significantly recovered in 4-week-old scar tissue. Steady state distribution volume (ΔR1 relaxation rate) of Gd-DTPA was markedly higher in scarred myocardium than in normal myocardium, whereas ΔR1 relaxation rate of P792 did not differ significantly between scarred and normal myocardium. The ratio of extracellular volume to the total water volume was significantly greater in scarred myocardium than in normal myocardium. Scarred myocardium contained massive residual capillaries and dilated vessels. Histological stains indicated the extensively discrete matrix deposition and lack of cellular structure in scarred myocardium.
  
  
  CONCLUSIONS
  Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd-DTPA rather than P792 to penetrate into extravascular compartment. Discrete collagen fiber meshwork and loss of cellularity enlarged extracellular space accessible to Gd-DTPA, resulting in the delayed hyper-enhanced scar.
authors.affiliation: Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; National Research Council, Winnipeg, Manitoba, Canada; Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Cardiac Surgery, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Research Council, Winnipeg, Manitoba, Canada; Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.affiliation: National Research Council, Winnipeg, Manitoba, Canada.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Cardiac Surgery, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: National Research Council, Winnipeg, Manitoba, Canada; Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Cardiac Science Program, Institute of Cardiovascular Sciences, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
authors.forename: Darren
authors.initials: D
authors.lastname: Freed
authors.affiliation: National Research Council, Winnipeg, Manitoba, Canada; Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Cardiac Science Program, Institute of Cardiovascular Sciences, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Arora
authors.affiliation: National Research Council, Winnipeg, Manitoba, Canada; Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ganghong
authors.initials: G
authors.lastname: Tian
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000473:pathology*; D003287:Contrast Media / Q000008:administration & dosage*; D053805:Fractional Flow Reserve, Myocardial; D005682:Gadolinium / Q000008:administration & dosage; D019786:Gadolinium DTPA / Q000008:administration & dosage; D006321:Heart / Q000503:physiopathology*; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D055806:Microvessels / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D013552:Swine
chemical_list: D003287:Contrast Media; D005682:Gadolinium; D019786:Gadolinium DTPA