Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex.
Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look-Locker-based quantitative T(1) mapping, and T(1) -weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2-4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration.
Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
Gisela E
GE
Hagberg
Ilgar
I
Mamedov
Anthony
A
Power
Michael
M
Beyerlein
Hellmut
H
Merkle
Valerij G
VG
Kiselev
Kirti
K
Dhingra
Vojtĕch
V
Kubìček
Goran
G
Angelovski
Nikos K
NK
Logothetis
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D003287:Contrast Media; D004058:Diffusion; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011859:Radiography; D051381:Rats
D003287:Contrast Media; D002118:Calcium
MRI; brain; diffusion; extracellular calcium; responsive contrast agent