Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo

Abstract

Background: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H₂ O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking.

Purpose: Validate theory describing blood behavior of R₁ and R₂ * in an animal model.

Study type: Prospective, animal.

Animal model: Seven swine (54-65 kg).

Field strength/sequence: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences.

Assessment: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R₁ and R₂ * effects (whole-blood model) and simpler models incorporating linear R₁ , with and without R₂ * effects. Predicted SIs were compared to measured aortic SI.

Statistical tests: Linear correlation (coefficient of determination, R² ) and mean errors were compared across the SI prediction models.

Results: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R₁ and high blood R₂ * (regression slopes 0.91-1.04, R² ≥ 0.91). Simplified models (linear R₁ with and without R₂ * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R² ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively).

Data conclusion: Incorporating sub-linear R₁ and high first-pass R₂ * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI.

Level of evidence: 1 TECHNICAL EFFICACY: Stage 1.

Keywords: contrast-enhanced MR angiography; gadolinium-based contrast agent; gadolinium-based contrast agent relaxivity.