MR imaging assessment of the kinetics of P846, a new gadolinium-based MR contrast medium, in ischemically injured myocardium.
The objectives of the study were: (1) to compare the kinetics of a new gadolinium-based low-diffusibility magnetic resonance (MR) contrast medium, P846 and Gd-DOTA in left ventricular (LV) blood and in normal and ischemically injured myocardium using inversion recovery echo-planar imaging (IR-EPI) and (2) to compare the enhancement pattern after injection of P846 with Gd-DOTA, using T1-weighted spin-echo imaging (T1-SE). Sixteen rats were subjected to left descending artery (LAD) occlusion for 30 min, followed by 2.5 h reperfusion. MR imaging was performed before and after administration of the contrast medium in two different groups of animals: one group (n = 8) received 0.05 mmol kg(-1) P846 and the other (n = 8) 0.1 mmol kg(-1) Gd-DOTA. A blipped IR-EPI and a multislice T1-SE were performed before injection and for 90 min after injection. T1-values were derived by fitting regional signal intensity on the IR-EPI images, the R1, DeltaR1 (R(1postcontrast) - R(1precontrast)) and DeltaR1 ratios were calculated in LV blood, normal and injured myocardium. On SE-T(1), the signal intensity ratio (SI) and extent of injury were measured. True infarct size was measured using histochemical staining. Changes in DeltaR(1) were 4.8 times greater with 0.05 mmol kg(-1) P846 than with 0.1 mmol kg(-1) Gd-DOTA in LV blood (6.3 +/- 0.9 vs 0.9 +/- 0.1 s(-1), p < 0.0001), normal (1.7 +/- 0.2 vs 0.34 +/- 0.03 s(-1), p < 0.0001) and ischemically injured myocardium (5.4 +/- 0.4 vs 1.6 +/- 0.1 s(-1), p < 0.0001). MR imaging experiments showed that the signal enhancement with P846 is longer (90 min), which might be explained by a lower diffusion of P846 compared with Gd-DOTA (30 min). P846 differentiates viable and nonviable myocardium. Despite lower gadolinium dose, P846 permits differentiation of viable and nonviable myocardium owing to a high contrast and a long imaging window with conventional t1-weighted SE sequence.
Department of Radiology, University of California San Francisco, CA 94134-0628, USA.
Alexis
A
Jacquier
Michael
M
Wendland
Loi
L
Do
Philippe
P
Robert
Claire
C
Corot
Charles B
CB
Higgins
Maythem
M
Saeed
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D004058:Diffusion; D017352:Echo-Planar Imaging; D005682:Gadolinium / Q000493:pharmacokinetics*; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D007089:Image Enhancement; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C531154:P846 compound; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium