title: Monitoring angiogenesis in brain using steady-state quantification of DeltaR2 with MION infusion.
abstract: An MRI method for quantification of cerebral blood volume (CBV) in time-course studies of angiogenesis is described. Angiogenesis was stimulated by acclimation to hypoxia. The change in relaxation rate, R2, which is relatively sensitive to the microvasculature, was quantified before and after infusion of a superparamagnetic vascular contrast agent (MION). The DeltaR2 was measured in serum and brain parenchyma with a multiecho sequence. In vitro and in vivo calibration curves of MION concentration vs. R2 were approximated by a linear function. CBV was 3.14 +/- 0.32% (mean +/- SE, n=13) and 6.42 +/- 0.54% (n=4) before and after acclimation. A second acclimated group was hemodiluted to control for polycythemia. CBV was not significantly different between hemodiluted and nonhemodiluted groups. In animals where NMR measurements were taken before and after acclimation, there was a 120% increase in CBV. The NMR technique was validated using quantitative morphometrics, which showed an increase of 147% in CBV with acclimation. We found a linear correlation between MRI and the morphometric results for CBV, as well as demonstrating a quantitative equivalence for relative changes in CBV. This article describes a simple, repeatable method of imaging brain microvascular volume using a plasma-based contrast agent that can be applied to longitudinal studies of angiogenesis.
authors.affiliation: Department of Radiology, Dartmouth Medical School, HB 7786, Hanover, New Hampshire 03755, USA. jeffrey.f.dunn@dartmouth.edu
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Dunn
authors.forename: Marcie A
authors.initials: MA
authors.lastname: Roche
authors.forename: Roger
authors.initials: R
authors.lastname: Springett
authors.forename: Michelle
authors.initials: M
authors.lastname: Abajian
authors.forename: Jennifer
authors.initials: J
authors.lastname: Merlis
authors.forename: Charles P
authors.initials: CP
authors.lastname: Daghlian
authors.forename: Shi Y
authors.initials: SY
authors.lastname: Lu
authors.forename: Malek
authors.initials: M
authors.lastname: Makki
mesh_terms: D000818:Animals; D001810:Blood Volume; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D002534:Hypoxia, Brain / Q000473:pathology*; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008856:Microscopy, Fluorescence; D009010:Monte Carlo Method; D009389:Neovascularization, Pathologic; D010087:Oxides; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide