Assessing permeability alterations of the blood-bone marrow barrier due to total body irradiation:: in vivo quantification with contrast enhanced magnetic resonance imaging

Our aim was to quantify irradiation-induced permeability alterations of the blood-bone marrow barrier (BMB) with dynamic contrast enhanced magnetic resonance imaging (MRI). The standard small molecular contrast agent, gadoterate meglumine, and a new macromolecular contrast agent, carboxymethyldextran-Gd-DOTA (CMD-Gd-DOTA), were compared. Twenty New Zealand white rabbits underwent MRI of the bone marrow before and 1-2 days after total body irradiation (TBI), Dynamic, repetitive T1-weighted MRI was performed before and after injection of either 0.05 mmol/kg BW CMD-Gd-DOTA (n = 10) or 0.5 mmol/kg BW gadoterate (n = 10). Bone marrow contrast enhancement was quantified as delta signal intensity: Delta SI = \(SIpost - SIpre) / SIpre\ * 100%. All MRI data were compared with the histopathologic BMB ultrastructure. Dynamic bone marrow Delta SI data steadily increased after CMD-Gd-DOTA injection, while blood Delta SI data slightly decreased, This hone marrow contrast enhancement, indicative of contrast agent extravasation, was significantly higher and prolonged in the irradiated group as compared to non-irradiated controls (P < 0.05) and corresponded to irradiation-induced alterations of the BMB ultrastructure seen on electron microscopy. By contrast, Delta SI data of non-irradiated and irradiated marrow were not significantly different following gadoterate injection (P > 0.05). We conclude that irradiation-induced alterations in BMB permeability could be reliably assessed with dynamic MRI, using the new macromolecular contrast agent CMD-Gd-DOTA.