Assessing permeability alterations of the blood-bone marrow barrier due tototal 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 re sonance imaging (MRI). The standard small molecular contrast agent, gadoter ate meglumine, and a new macromolecular contrast agent, carboxymethyldextra n-Gd-DOTA (CMD-Gd-DOTA), were compared. Twenty New Zealand white rabbits un derwent MRI of the bone marrow before and 1-2 days after total body irradia tion (TBI), Dynamic, repetitive T1-weighted MRI was performed before and af ter 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 enh ancement, indicative of contrast agent extravasation, was significantly hig her and prolonged in the irradiated group as compared to non-irradiated con trols (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 f ollowing gadoterate injection (P > 0.05). We conclude that irradiation-indu ced alterations in BMB permeability could be reliably assessed with dynamic MRI, using the new macromolecular contrast agent CMD-Gd-DOTA.