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: ΔSI = |(SIpost − SIpre) / SIpre| * 100%. All MRI data were compared with the histopathologic BMB ultrastructure. Dynamic bone marrow ΔSI data steadily increased after CMD-Gd-DOTA injection, while blood ΔSI 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, ΔSI 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.
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References
Stevens S, Moore S, Amylon M . Repopulation of marrow after transplantation: MR imaging with pathologic correlation Radiology 1990 175: 213–218
Shirota T, Tavassoli M . Alterations of bone marrow sinus endothelium induced by ionizing irradiation: implications in the homing of intravenously transplanted marrow cells Blood Cells 1992 18: 197–214
Tavassoli M, Yoffey J (eds) . Blood–marrow barrier. In: Bone Marrow Structure and Function AR Liss: New York 1983 pp 85–102
Hudson G, Yoffey J . Ultrastructure of reticuloendothelial elements in guinea pig bone marrow J Anat 1968 103: 515–525
Bankstrom P, DeBruyn P . The permeability to carbon of the sinusoidal lining cells of the embryonic rat liver and rat bone marrow Am J Anat 1974 141: 281–290
Moore S, Dawson K . Red and yellow marrow in the femur: age related changes in appearance at MRI Radiology 1990 175: 219–223
Cova M, Kang Y, Tsukamoto H et al. Bone marrow perfusion evaluated with gadolinium-enhanced dynamic fast MR imaging in a dog model Radiology 1991 179: 535–539
Gerard E, Ferry J, Amrein P et al. Compositional changes in vertebral bone marrow during treatment for acute leukemia: assessment with quantitative chemical shift imaging Radiology 1992 183: 39–46
Kauczor H, Brix G, Dietl B et al. Bone marrow after autologous blood stem cell transplantation and total body irradiation: magnetic resonance and chemical shift imaging Mag Res Imag 1993 11: 965–975
Saifuddin A, Bann K, Ridgway J, Butt W . Bone marrow blood supply in gadolinium-enhanced magnetic resonance imaging Skel Radiol 1994 23: 455–457
Sugimura H, Kisanuki A, Tamura S et al. Magnetic resonance imaging of bone marrow changes after irradiation Invest Rad 1994 29: 35–41
Altehoefer C, Blum U, Bathmann J et al. Comparative diagnostic accuracy of magnetic resonance imaging and immunoscintigraphy for detection of bone marrow involvement in patients with malignant lymphoma J Clin Oncol 1997 15: 1754–1760
Berthezene Y, Vexler V, Kuwatsuru R et al. Differentiation of alveolitis and pulmonary fibrosis with a macromolecular MR imaging contrast agent Radiology 1992 185: 97–103
Brasch R . New directions in the development of MR imaging contrast media Radiology 1992 183: 1–11
Brasch R, Pham C, Shames D et al. Assessing tumor angio-genesis using macromolecular MR imaging contrast media J Magn Res Imaging 1997 7: 68–74
Daldrup H, Shames D, Wendland M et al. Correlation of dynamic contrast-enhanced magnetic resonance imaging with histologic tumor grade: comparison of macromolecular and small molecular contrast media AJR 1998 28: 67–78
Cohen F, Kawatsuru R, Shames D et al. Contrast enhanced MRI estimation of altered capillary permeability in experimental mammary carcinomas following X-irradiation Invest Radiol 1995 29: 970–977
Schwickert H, Stiskal M, Roberts T et al. Contrast enhanced MR imaging of tumor capillary permeability: effect of irradiation on delivery of chemotherapy Radiology 1996 198: 893–898
Bousquet J, Saini S, Stark D et al. Gd-DOTA: characterization of a new paramagnetic complex Radiology 1988 166: 693–698
Corot C, Schaefer M, Beaute S et al. Physical, chemical and biologic evaluations of CMD-A2-Gd-DOTA. A new paramagnetic dextran polymer Acta Radiol 1997 412: (Suppl.) 91–99
Shames D, Kuwatsuru R, Vexler V et al. Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: a quantitative non-invasive technique Magn Res Med 1993 29: 616–622
Brasch R, Shames D, Cohen F et al. Quantification of capillary permeability to macromolecular magnetic resonance imaging contrast media in experimental mammary adenocarcinomas Invest Radiology 1994 29: 1–4
Dvorak H, Nagy J, Dvorak J, Dvorak A . Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules Am J Pathol 1988 133: 95–109
Prato F, Wisenberg G, Marshall T et al. Comparison of the biodistribution of gadolinium-153 DTPA and technetium-99m DTPA in rats J Nucl Med 1988 29: 1683–1687
Wedeking P, Eaton S, Covell D et al. Pharmacokinetic analysis of blood distribution of intravenously administered 153Gd-labeled Gd(DTPA)2- and 99mTc(DTPA) in rats Mag Res Imag 1990 8: 567–575
Tong C, Prato S, Wisenberg G et al. Measurement of the extraction efficiency and distribution volume for Gd-DTPA in normal and diseased canine myocardium Magn Res Med 1993 30: 337–346
Montgomery P, Karney D, Reynolds R, McLendon D . Cellular and subcellular effects of ionizing radiations Am J Pathol 1964 44: 727–733
Stefani S, Chandra S, Tonaki H . Ultrastructural events in the cytoplasmatic death of lethally-irradiated human lymphocytes Int J Radiat Biol 1977 31: 215–225
Wallach D . Radiation effects on biomembranes Biomembranes 1974 5: 213–249
Leyko W, Bartosz G . Membrane effects of ionizing radiation and hyperthermia Int J Radiat Biol 1986 49: 743–770
Papayannopoulou T, Craddock C . Homing and trafficking of hematopoietic progenitor cells Acta Hematol 1997 97: 97–104
Jaramillo D, Shapiro F, Hoffer F et al. Posttraumatic growth plate abnormalities: MR imaging of bony-bridge formation in rabbits Radiology 1990 175: 767–773
Seneterre E, Weissleder R, Jaramillo D et al. Bone marrow: utrasmall superparamagnetic iron oxide for MR imaging Radiology 1991 179: 529–533
Shirota T, Tavassoli M . Cyclophosphamide-induced alterations of bone marrow endothelium: implications in homing of marrow cells after transplantation Exp Hematol 1991 19: 369–373
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This work was supported by German Cancer Research Foundation grant (Dr Mildred Scheel Stiftung) D/96/17149, No. 683 400 001.
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Daldrup-Link, H., Link, T., Rummeny, E. et al. Assessing permeability alterations of the blood–bone marrow barrier due to total body irradiation: in vivo quantification with contrast enhanced magnetic resonance imaging. Bone Marrow Transplant 25, 71–78 (2000). https://doi.org/10.1038/sj.bmt.1702087
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DOI: https://doi.org/10.1038/sj.bmt.1702087
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