Using MRI to Determine Drug Concentration in Convection-Enhanced Delivery: A Proof-of-Concept study

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Convection-enhanced delivery (CED) bypasses the blood-brain barrier, but systemic pharmacokinetics do not apply.
• Evaluating drug distribution and concentration after CED requires specialized methods.
• Noninvasive techniques are needed to assess drug pharmacokinetics in the brain following CED.

Purpose of the Study:

• To establish a proof-of-concept framework for noninvasively evaluating pharmacokinetics in CED using MRI.
• To quantify the local concentration and distribution of a gadolinium-based contrast agent (Gd-DTPA) in rat brains.
• To correlate MRI-derived data with known Gd-DTPA concentrations.

Main Methods:

• Utilized a 7.0 T MRI system to scan Gd-DTPA standards in rat brain tissue suspension.
• Calculated T1 relaxivity of Gd-DTPA from T1-mapped images.
• Administered Gd-DTPA into the rat striatum, followed by in vivo T1 mapping to determine voxel-level concentrations and construct concentration maps.

Main Results:

• A linear relationship (R² = 0.9919) was observed between Gd-DTPA concentration and 1/T1 in tissue suspension.
• The T1 relaxivity of Gd-DTPA was determined to be 4.199 mM⁻¹s⁻¹.
• The mean volume of distribution to initial volume ratio (Vd/Vi) was 6.02, with decreasing concentration at the infusion center and stable peripheral concentrations.

Conclusions:

• MRI can accurately and reliably determine Gd-DTPA concentration and spatial distribution in rat brains after CED.
• The developed framework enables noninvasive pharmacokinetic assessment for CED-treated brain tissue.
• This approach provides crucial data on drug distribution and temporal changes within the brain parenchyma.