scholarly journals How Stereological Analysis of Vascular Morphology Can Quantify the Blood Volume Fraction as a Marker for Tumor Vasculature: Comparison with Magnetic Resonance Imaging

2011 ◽  
Vol 32 (3) ◽  
pp. 489-501 ◽  
Author(s):  
Adriana T Perles-Barbacaru ◽  
Boudewijn PJ van der Sanden ◽  
Regine Farion ◽  
Hana Lahrech

To assess angiogenesis noninvasively in a C6 rat brain tumor model, the rapid-steady-state- T1 (RSST1) 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 ( VV). The VV 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 RSST1-MRI with Gd-ACX. The mean perfused VV and the BVf obtained by MRI in tumor regions are practically equal and the technique confirms the spatial heterogeneity revealed by MRI.

2002 ◽  
Vol 22 (3) ◽  
pp. 262-270 ◽  
Author(s):  
Mikko I. Kettunen ◽  
Olli H. J. Gröhn ◽  
M. Johanna Silvennoinen ◽  
Markku Penttonen ◽  
Risto A. Kauppinen

The balance between oxygen consumption and delivery in the rat brain after exposure to transient ischemia was quantitatively studied with single-spin echo T2-BOLD (blood oxygenation level–dependent) magnetic resonance imaging at 4.7 T. The rats were exposed to graded common carotid artery occlusions using a modification of the four-vessel model of Pulsinelli. T2, diffusion, and cerebral blood volume were quantified with magnetic resonance imaging, and CBF was measured with the hydrogen clearance method. A transient common carotid artery occlusion below the CBF value of approximately 20 mL·100 g−1·min−1 was needed to yield a T2 increase of 4.6 ± 1.2 milliseconds (approximately 9% of cerebral T2) and 6.8 ± 1.7 milliseconds (approximately 13% of cerebral T2) after 7 and 15 minutes of ischemia, respectively. Increases in CBF of 103 ± 75% and in cerebral blood volume of 29 ± 20% were detected in the reperfusion phase. These hemodynamic changes alone could account for only approximately one third of the T2 increase in luxury perfusion, suggesting that a substantial increase in blood oxygen saturation (resulting from reduced oxygen extraction by the brain) is needed to explain the magnetic resonance imaging observation.


NeuroImage ◽  
2003 ◽  
Vol 20 (3) ◽  
pp. 1591-1600 ◽  
Author(s):  
Trygve B Leergaard ◽  
Jan G Bjaalie ◽  
Anna Devor ◽  
Lawrence L Wald ◽  
Anders M Dale

2008 ◽  
Vol 28 (5) ◽  
pp. 1017-1029 ◽  
Author(s):  
Hana Lahrech ◽  
Adriana-Teodora Perles-Barbacaru ◽  
Soâd Aous ◽  
Jean-François Le Bas ◽  
Jean-Claude Debouzy ◽  
...  

In magnetic resonance imaging (MRI), cerebral blood volume (CBV) quantification is dependent on the MRI sequence and on the properties of the contrast agents (CAs). By using the rapid steady-state T1 method, we show the potential of gadolinium per (3,6-anhydro) α-cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd3+ with per (3,6-anhydro)-α-cyclodextrin), for the CBV quantification in the presence of blood—brain barrier lesions. After biocompatibility and relaxivity experiments, in vivo experiments on rats were performed on a C6 tumor model with 0.05 mmol Gd-ACX/kg (<1/10 of the median lethal dose) injected at a 25mmol/L concentration, inducing neither nephrotoxicity nor hemolysis. On T1-weighted images, a signal enhancement of 170% appeared in vessels after injection, but not in the tumor (during the 1 h of observation), in contrast to the 90% signal enhancement obtained with Gd-DOTA (a clinical MRI CA) injected at a T1 isoefficient dose. This result shows the absence of Gd-ACX extravasation into the tumor tissue and its confinement to the vascular space. Fractional CBV values were found similar to Gd-ACX and Gd-DOTA in healthy brain tissue and in the contralateral hemisphere of tumor-bearing rats, whereas only Gd-ACX was appropriate for CBV quantification in tumor regions.


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