title: NMR imaging of changes in vascular morphology due to tumor angiogenesis.
abstract: Tumor-sprouted vessels are greater in both number and diameter in comparison to their healthy counterparts. A novel technique based on magnetic susceptibility contrast mechanisms that are sensitive to varying sizes of blood vessels is presented to measure differences between the relaxation rates (1/T2 and 1/T2*) in a rat glioma model and normal cerebral cortex. deltaR2 and deltaR2*, the differences between relaxation rates precontrast and postcontrast agent injection, were measured for an intravascular equilibrium contrast agent (MION) at various echo times. Since deltaR2*/deltaR2 increases as vessel size increases, this ratio can be used as a measure of the average vessel size within an ROI or a voxel. The stability and longevity of the contrast agent within the vasculature were verified (n = 2 trials), and the ratio of deltaR2*/deltaR2 between the tumor and normal cortex was measured to be 1.9+/-0.2 (n = 4, echo time = 20 ms, and susceptibility difference (deltachi) approximately 10(-6)). This ratio compared favorably to a predicted ratio determined using histologically determined vessel sizes and theoretical Monte Carlo modeling results (1.9+/-0.1). Maps of the ratio of deltaR2*/deltaR2 were also made on a pixel-by-pixel basis. These techniques support the hypothesis that susceptibility contrast MRI can provide useful quantitative metrics of in vivo tumor vascular morphology.
authors.affiliation: MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dennie
authors.forename: J B
authors.initials: JB
authors.lastname: Mandeville
authors.forename: J L
authors.initials: JL
authors.lastname: Boxerman
authors.forename: S D
authors.initials: SD
authors.lastname: Packard
authors.forename: B R
authors.initials: BR
authors.lastname: Rosen
authors.forename: R M
authors.initials: RM
authors.lastname: Weisskoff
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D019786:Gadolinium DTPA; D005910:Glioma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007501:Iron; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D009010:Monte Carlo Method; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010087:Oxides; D011897:Random Allocation; D051381:Rats
chemical_list: D003287:Contrast Media; D010087:Oxides; D007501:Iron; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide