In vivo myocardial tissue kinetics of Gd(ABE-DTTA), a tissue-persistent contrast agent.

The phenomenological tissue kinetics of Gd(ABE-DTTA) was investigated in myocardial infarction (MI). Reperfused infarction was generated by balloon catheter in closed-chest canines (N=11). Forty-eight hours thereafter, inversion-recovery (IR)-prepared fast gradient-echo control images were acquired with varying inversion times (TIs). Precontrast R(1) maps were calculated from the TI dependence of signal intensity (SI) using nonlinear curve fitting. Then 0.05 mmol/kg Gd(ABE-DTTA) was administered I.V. In 11 dogs postcontrast R(1) maps were generated at 24 hr and 48 hr postcontrast. In five dogs measurements were also repeated at 108 hr and 12 days. In one dog early measurement was carried out at 4 hr. Delta R(1) values for blood and viable and infarcted myocardium were calculated at each time point by subtracting the precontrast R(1) from the postcontrast R(1). Gd(ABE-DTTA) showed significant, progressive accumulation into infarcts during the first 2 days (k(in)=0.39 hr(-1)) and a delayed clearance (k(out) = 0.005 hr(-1)). Among the time points sampled, the maximum infarct Delta R(1) was detected at 48 hr (1.72 s(-1)). Contrast agent (CA) in infarcted tissue was detectable for 12 days. Clearance from blood and viable myocardium occurred in parallel and was completed by 108 hr. Gd(ABE-DTTA) displays slow, tissue-persistent kinetics and partly intravascular, partly extravascular characteristics. It demonstrates high affinity for infarcted myocardium and induces highlighting of infarcts between 4 hr and 12 days following administration.

Percent infarct mapping: an R1-map-based CE-MRI method for determining myocardial viability distribution.

Viability detection is crucial for the management of myocardial infarction (MI). Signal intensity (SI)-based MRI methods may overestimate infarct size in vivo. In contrast to SI, the longitudinal relaxation-rate enhancement (DeltaR1) is an intrinsic parameter that is linearly proportional to the concentration of contrast agent (CA). Determining DeltaR1 in the presence of an infarct-avid persistent CA (PCA) allows determination of the per-voxel percentage of infarcted tissue. Introduced here is a DeltaR1-based CE-MRI method, termed percent infarct mapping (PIM), for quantifying myocardial viability following delayed PCA accumulation. In a canine MI model (N=6), PIMs were generated using a persistent CA (PCA) and validated using triphenyltetrazolium-chloride (TTC) histochemistry. Voxel-by-voxel R1 maps of the entire left ventricle (LV) were generated 24 and 48 hr after PCA administration using inversion recovery (IR) with multiple inversion times (TIs). PI values were calculated voxel by voxel. Significant correlations (P<0.01, R=0.97) were obtained for PI per slice (PIS) determined using PIM vs. corresponding TTC-based values. Median deviations of PIS with PIM from that with TTC were only 1.01% and -0.53%, at 24 hr and 48 hr. Median deviations from the true infarction fraction (IF) were 1.23% and 0.49% of LV at 24 hr and 48 hr, respectively. No significant difference was found between PIM24 hr and PIM48 hr. DeltaR1-based PIM is an accurate and reproducible method for quantifying myocardial viability distribution, and thus enhances the clinical utility of CE-MRI.

Gd(ABE-DTTA), a novel contrast agent, at the MRI-effective dose shows absence of deleterious physiological effects in dogs.

The physiological effects of a novel MRI contrast agent, Gd(ABE-DTTA), were investigated in dogs, monitoring parameters in blood samples. Each animal (n = 8 in the short-term, n = 4 in the long-term group) underwent isoflurane anesthesia followed by the generation of myocardial infarction and received a contrast agent at the MRI effective dose. Blood samples were collected 24 and 48 h, and 7, 14, 28, 35, 49 and 56 days after contrast agent administration. No significant changes exceeding the normal range were detected in any of the investigated parameters except in alanine aminotransferase (ALT). ALT enzyme activity increased in the short-term group 24 and 48 h after agent administration as expected from the effect of isoflurane anesthesia. Between days 7 and 56 no elevation in ALT was observed. In dogs no substantial short- or long-term effect was observed on the investigated, physiological parameters after Gd(ABE-DTTA) administration at the MRI effective dose.