Monitoring radiation-induced changes in bone marrow histopathology with ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI

The purpose of this study was to monitor radiation-induced alterations of t he blood-bone marrow barrier (BMB) and the reticuloendothelial system (RES) with AMI-227-enhanced magnetic resonance imaging (MRI). Twenty New Zealand white rabbits (n = 10 following total body irradiation and n = 10 controls ) underwent AMI-227-enhanced NW, Pulse sequences included dynamic fast low- angle shot (FLASH: TR/TE 50/4 msec, hip angle 60 degrees) MRI and static T1 - and T2-weighted spin-echo (SE) and turbo-SE sequences of the lumbar spine and sacrum, Bone marrow enhancement was quantified as Delta signal intensi ty (SI) (%) = \[(SIpost - SIpre)/SIpre] x 100%\ and compared with histopath ology, including iron stains and electron microscopy. Dynamic bone marrow D elta SI (%) data steadily increased up to 10-15 minutes after AMI-227 admin istration, while blood Delta SI (%) data stayed nearly constant, histologic ally correr spending to iron oxide leakage into the bone marrow interstitiu m. This bone marrow contrast enhancement increased significantly following irradiation, corresponding to alterations of the endothelial lining of the bone marrow sinusoids. Late postcontrast images exhibited a significant pos itive T1 enhancement and negative T2 enhancement of the normal bone marrow, which further increased with irradiation due to increased RES activity. Ir radiation-induced changes in bone marrow physiology could be reliably asses sed with AMI-227-enhanced MRI. (C) 1999 Wiley-Liss, Inc.