Volume 25, Issue 1, Page 71

Bone Marrow Transplantation
January 2000, Volume 25, Issue 1, Pages 71 – 78

Title

Abstract

Keywords

Title

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

HE Daldrup-Link¹, TM Link¹, EJ Rummeny¹, C August², S Könemann³, H Jürgens⁴ & W Heindel¹

¹Department of Clinical Radiology, University of Münster, Münster, Germany
²Department of Pathology, University of Münster, Münster, Germany
³Department of Radio-Oncology, University of Münster, Münster, Germany
⁴Department of Pediatric Oncology, University of Münster, Münster, Germany

Correspondence to: Dr HE Daldrup-Link, Department of Clinical Radiology, University of Münster, Albert-Schweitzer-Str.33, D-48129 Münster, Germany

Abstract

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: SI = |(SI_post – SI_pre) / SI_pre| * 100%. All MRI data were compared with the histopathologic BMB ultrastructure. Dynamic bone marrow SI data steadily increased after CMD-Gd-DOTA injection, while blood SI data slightly decreased. This bone 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, 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. Bone Marrow Transplantation (2000) 25, 71–78.

Keywords

blood–bone marrow barrier; MRI; macromolecular contrast agents

Received 13 April 1999; Accepted 1 August 1999