title: How stereological analysis of vascular morphology can quantify the blood volume fraction as a marker for tumor vasculature: comparison with magnetic resonance imaging.
abstract: To assess angiogenesis noninvasively in a C6 rat brain tumor model, the rapid-steady-state-T(1) (RSST(1)) magnetic resonance imaging (MRI) method was used for microvascular blood volume fraction (BVf) quantification with a novel contrast agent gadolinium per (3,6 anhydro) α-cyclodextrin (Gd-ACX). In brain tissue contralateral to the tumor, equal BVfs were obtained with Gd-ACX and the clinically approved gadoterate meglumine (Gd-DOTA). Contrary to Gd-DOTA, which leaks out of the tumor vasculature, Gd-ACX was shown to remain vascular in the tumor tissue allowing quantification of the tumor BVf. We sought to confirm the obtained tumor BVf using an independent method: instead of using a 'standard' two-dimensional histologic method, we study here how vascular morphometry combined with a stereological technique can be used for three-dimensional assessment of the vascular volume fraction (V(V)). The V(V) is calculated from the vascular diameter and length density. First, the technique is evaluated on simulated data and the healthy rat brain vasculature and is then applied to the same C6 tumor vasculature previously quantified by RSST(1)-MRI with Gd-ACX. The mean perfused V(V) and the BVf obtained by MRI in tumor regions are practically equal and the technique confirms the spatial heterogeneity revealed by MRI.
authors: Université Joseph Fourier, Grenoble Institut des Neurosciences, Grenoble, France. adriana.perles@ujf-grenoble.fr
authors: Adriana T
authors: AT
authors: Perles-Barbacaru
authors: Boudewijn P J
authors: BP
authors: van der Sanden
authors: Regine
authors: R
authors: Farion
authors: Hana
authors: H
authors: Lahrech
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000502:physiology*; D001811:Blood Volume Determination / Q000379:methods*; D001931:Brain Mapping; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D003287:Contrast Media; D005910:Glioma / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D006571:Heterocyclic Compounds; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000473:pathology* / Q000503:physiopathology; D008953:Models, Anatomic; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D009942:Organometallic Compounds; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate