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Application of MRI phase-difference mapping to assessment of vascular concentrations of BMS agent in mice
Emeline Julie Ribot1, Eric Thiaudière, Richard Roulland
1Magnetic Resonance Center, CNRS-Victor Segalen University of Bordeaux 2, Bordeaux, France.
Abstract:
Direct quantitation of contrast agent concentration can be performed using dynamic susceptibility contrast MRI. This method is based on phase imaging and administration of paramagnetic agents such as gadolinium-chelates. This technique has only been applied on humans or primates. However, numerous research models have been developed on small animals like mice. For this reason, the aim of this work was the application of this MRI technique, allowing the direct quantitation of the contrast agent concentrations in vivo, in the mouse vascular system at high field. For this purpose, Dy-DOTA has been preferred to Gd-DOTA due to a lower T(2)* effect. Dy-DOTA shifts in Larmor frequency were measured by phase difference mapping, using fast gradient-echo imaging at short echo times. Such an acquisition sequence allowed the limitation of susceptibility artifacts at high magnetic fields and phase wrapping. As demonstrated in a phantom oriented parallel to the static magnetic field, it is possible to measure contrast agent concentrations between 0 and 10 mm with an uncertainty of about 100 microm. Finally, the method was applied on living mice at 4.7 T. After the bolus injection, the evolution of contrast agent concentrations was assessed in brain blood vessels parallel to B(0). Long-term disappearance of contrast agent was monitored at high spatial resolution every 15 s. Alternatively, lower resolved images at 0.72 s time-resolution allowed preliminary assessment of arterial input functions. The feasibility of quantitative bolus-tracking in small rodents opens the way for comprehensive descriptions of flow and over time-dependent biological processes, especially in pathological murine models.
Insights
This study introduces a new MRI method for precisely measuring contrast agent concentration in mouse blood vessels. This technique enables detailed analysis of biological processes in small animal models.
Area of Science:
- Medical Imaging
- Biophysics
- Pharmacokinetics
Background:
- Dynamic susceptibility contrast MRI quantifies contrast agent concentration using phase imaging and paramagnetic agents.
- Current applications are limited to humans and primates, hindering research in small animal models.
- Developing techniques for small animals is crucial for advancing preclinical research.
Purpose of the Study:
- To adapt dynamic susceptibility contrast MRI for direct, in vivo quantitation of contrast agent concentrations in the mouse vascular system at high magnetic fields.
- To evaluate the feasibility of using Dy-DOTA over Gd-DOTA for improved accuracy and reduced artifacts.
- To establish a method for high-resolution, time-resolved monitoring of contrast agent dynamics in mice.
Main Methods:
- Utilized fast gradient-echo imaging with short echo times and phase difference mapping to measure Larmor frequency shifts caused by Dy-DOTA.
- Employed a specialized acquisition sequence to minimize susceptibility artifacts and phase wrapping in high-field MRI.
- Validated the method in phantoms for precise concentration measurements (0-10 mm range, ~100 microm uncertainty).
Main Results:
- Successfully applied the quantitative MRI technique in living mice at 4.7 T.
- Monitored the evolution and long-term disappearance of contrast agent concentrations in mouse brain blood vessels with high spatial resolution (15 s intervals).
- Preliminary assessment of arterial input functions was achieved with a temporal resolution of 0.72 s.
Conclusions:
- Demonstrated the feasibility of quantitative bolus-tracking MRI in small rodents.
- This technique opens new avenues for comprehensive, time-dependent analyses of biological processes in preclinical murine models.
- Enables detailed study of flow dynamics and pathological conditions in mice using MRI.
