Objectives: The purpose of this phantom study in human plasma was to characterize the signal enhancement properties of gadoquatrane under clinically relevant, highly standardized conditions in comparison to gadobutrol. Gadoquatrane is a novel high-relaxivity, extracellular macrocyclic gadolinium-based contrast agent (GBCA) currently in clinical development at a dose of 0.01 mmol/kg body weight (corresponding to 0.04 mmol Gd/kg). Materials and Methods: Three GBCA-dilution series in human plasma were prepared: 2 series with equimolar Gd concentrations (0-10 mmol Gd/mL) for gadoquatrane (0.4 mol Gd/L) and gadobutrol (1.0 mol Gd/L), and 1 series with 60% lower Gd concentrations for gadoquatrane (12 samples/series). For each series, signal intensity versus Gd concentration profiles were obtained using standard T1-weighted MRI pulse sequences at 1.5 T. In addition, the impact of sequence parameters was investigated (repetition and echo time for spin-echo sequences; flip angle for gradient-echo sequences). Results: The signal enhancement achieved with the 2 GBCAs depended on the Gd concentration and the pulse sequence. For all sequences tested, almost superimposable signal intensity profiles were found for gadobutrol and gadoquatrane, with 60% lower Gd concentrations for gadoquatrane. Sequence parameter variations affected both GBCAs in the same way. The optimal flip angles were equal for gadobutrol and gadoquatrane (60% reduced). Conclusions: The signal intensity profiles obtained in human plasma using standard clinical pulse sequences were almost superimposable for gadobutrol and gadoquatrane at 60% lower Gd concentrations. For clinical use, this means that the same pulse sequence parameters can be used for both GBCAs and that, essentially, the same signal enhancement can be expected from gadoquatrane at a dose of 0.04 mmol Gd/kg body weight as from gadobutrol at a dose of 0.1 mmol Gd/kg.