title: Hindered diffusion of MRI contrast agents in rat brain extracellular micro-environment assessed by acquisition of dynamic T1 and T2 maps.
abstract: The knowledge of brain tissues characteristics (such as extracellular space and tortuosity) represents valuable information for the design of optimal MR probes for specific biomarkers targeting. This work proposes a methodology based on dynamic acquisition of relaxation time maps to quantify in vivo MRI contrast agent concentration after intra-cerebral injection in rat brain. It was applied to estimate the hindered diffusion in brain tissues of five contrast agents with different hydrodynamic diameters (Dotarem(®) ≈ 1 nm, P846 ≈ 4 nm, P792 ≈ 7 nm, P904 ≈ 22 nm and Gd-based emulsion ≈ 170 nm). In vivo apparent diffusion coefficients were compared with those estimated in an obstacle-free medium to determine brain extracellular space and tortuosity. At a 2 h imaging timescale, all contrast agents except the Gd-based emulsion exhibited significant diffusion through brain tissues, with characteristic times compatible with MR molecular imaging (<70 min to diffuse between two capillaries). In conclusion, our experiments indicate that MRI contrast agents with sizes up to 22 nm can be used to perform molecular imaging on intra-cerebral biomarkers. Our quantification methodology allows a precise estimation of apparent diffusion coefficients, which is helpful to calibrate optimal timing between contrast agent injection and MRI observation for molecular imaging studies.
authors.affiliation: NeuroSpin, I2BM, Commissariat à l'Énergie Atomique, Gif-sur-Yvette, France.
authors.forename: B
authors.initials: B
authors.lastname: Marty
authors.forename: B
authors.initials: B
authors.lastname: Djemaï
authors.forename: C
authors.initials: C
authors.lastname: Robic
authors.forename: M
authors.initials: M
authors.lastname: Port
authors.forename: P
authors.initials: P
authors.lastname: Robert
authors.forename: J
authors.initials: J
authors.lastname: Valette
authors.forename: F
authors.initials: F
authors.lastname: Boumezbeur
authors.forename: D
authors.initials: D
authors.lastname: Le Bihan
authors.forename: F
authors.initials: F
authors.lastname: Lethimonnier
authors.forename: S
authors.initials: S
authors.lastname: Mériaux
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D003287:Contrast Media / Q000494:pharmacology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003287:Contrast Media