Quantification of haematomyocardial barrier permeability for polyacetate complexes of Gd in ishaemic and inflammatory myocardial damage
Purpose. We developed and applied for quantification of microvascular permeability in damaged myocardium a model - based approach employing the dynamic acquisition of magnetic resonance imaging of paramagnetic diffusion to damaged myocardium and kinetic Gjedde-Rutlend-Patlak (GRP) analysis of blood clearance of the contrast concomitantly with it’s rise in the damaged tissue, in ischemic or inflamed tissue. Material and methods. The model is based on the passive gradient-driven diffusion, unidirectional for first minutes after injection of the contrast, used as Gjedd- Rutland-Patlak technique. If the C<sub>myoc</sub> - depicts the concentration of the paramagnetic in the blood, and the C<sub>blood</sub> - means the blood level of the contrast agent, whereas the k<sub>blood-myocardium</sub> - is the index of diffusion of the contrast from blood to myocardium, then assuming the diffusion unidirectional for first minutes post injection we can plot the ratio {(C<sub>blood</sub>(t)dt)/ C<sub>blood</sub>} - as abscissa X, and {C<sub>myoc</sub>/ C<sub>blood</sub>} - as ordinata Y, k<sub>blood-myocardium</sub> can be obtained then from such linear plot as it’s slope. We substituted the concentrations themselves with the values of intensities of the echo-planar ECG-synchronized scans of the heart and validated this approach with comparison of MRI intensity data over LV cavity to Gd content in blood samples. MRI of the heart with contrast enhancement was carried out using dynamic scannig, after bolus injection of 2 ml of 0.5 M of paramagnetic contrast (Gadoversetamide - <sup>TM</sup>Optimark) per 10 Kg of BW. TR = 3.4 ms, TE = 1.7 ms, inversion time 176.0 ms, deviation angle = 40 deg, scanning field 38 х 38 cm, slice thickness = 8-10 мм, acqusition matrix 256 х 256, or 192 х 192, echo train length = 1. The groups of patients comprised twenty one persons with acute myocardial infarction treated clically successfully with intravenous thrombolysis and coronary stenting and also nine persons with firstly revealed inflammatory myocarditis. Uptake kinetics to the myocardium was imaged using protocols with fat supression for up to 12 minutes after bolus injection and then processed using RadiAnt software (Medixant, Poznan, Polska), and also original software for dynamic data analysis written using MATLAB 6.1 (SCILAB also), with output of plots of MRI signal intensities over time for various myocardial regions and also of GRP plots and calculation of k<sub>blood-myocardium</sub>. Results. The physiological sence of thek<sub>blood-myocardium</sub> diffusion koefficient means this value depicts the clearance of paramagnetic to myocardium, i.e. the amount of blood cleared from the paramagnetic due to paramagnetic’ diffusion to damaged myocardium, per minute, per unit of myocardial volume. The value of the k<sub>blood-myocardium</sub> diffusion koefficient was, respectively, as high as 3.09 ± 1.32 (2.36-11.9) ml/min/100 g of tissue, in myocardial infarction although treated successfully with thrombolysis and stenting (n = 21) and 1.78 ± 0.67 (0.50-2.42) ml/min/100 g of tissue - in inflammatory myocarditis damage of myocardium (n = 9); In normal controls k<sub>blood-myocardium</sub> was close to zero values and namely as low as 0.09 ± 0.06 (<0.2) (ml/min/100 g of tissue). Use of this dynamic protocol provided highly significant separation of ishemic and iflammatory conditions. Conclusion. Dynamic MRI echo-planar ECG-synchronised contrast-enhanced echo-planar study of the heart can be successfully carried out using both high- and middle-field MRI scanner. The model-based indexes of diffusion of paramagnetic to the infarction or inflammation are significantly different and deliver additional object-based characteristics of the vascular permeability of the damaged haematomyocardial barrier.