title: Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T1 mapping.
abstract: BACKGROUND
  Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T1 measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T1 mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T1 before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent.
  
  
  METHODS
  Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T1 maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T1 measurement was performed. Local ΔR1 values were compared with regional wall thickening determined by functional cine CMR and correlated to ex vivo Gd concentrations determined by ICP-MS.
  
  
  RESULTS
  Compared to control values, pre-contrast T1 of infarcted myocardium was slightly elevated, whereas T1 of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR1 values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), ΔR1 was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (r = 0.81) was found between CMR-based ΔR1 values and Gd concentrations from ex vivo ICP-MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined in vitro.
  
  
  CONCLUSIONS
  3D cardiac T1 mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under in vivo conditions compared to in vitro measurements, which needs consideration when quantifying local contrast agent concentrations.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO BOX 513, 5600MB, Eindhoven, the Netherlands.
authors.forename: Bram F
authors.initials: BF
authors.lastname: Coolen
authors.forename: Tessa
authors.initials: T
authors.lastname: Geelen
authors.forename: Leonie E M
authors.initials: LE
authors.lastname: Paulis
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D021621:Imaging, Three-Dimensional; D008081:Liposomes; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D003287:Contrast Media; D008081:Liposomes; C058946:albumin-(gadolinium-DTPA); D019786:Gadolinium DTPA