1: NMR Biomed. 2006 Feb;19(1):69-76. 

The role of vessel maturation and vessel functionality in spontaneous
fluctuations of T2*-weighted GRE signal within tumors.

Baudelet C, Cron GO, Ansiaux R, Crokart N, DeWever J, Feron O, Gallez B.

Laboratory of Biomedical Magnetic Resonance, Universite Catholique de Louvain,
Avenue E. Mounier 73.40, B-1200 Brussels, Belgium.

Acute hypoxia (transient cycles of hypoxia-reoxygenation) is known to occur in
solid tumors and is generally believed to be caused by tumor blood flow
instabilities. It was recently demonstrated that T2*-weighted (T2*w) gradient
echo (GRE) MRI is a powerful non-invasive method for investigating periodic
changes in tumor pO2 and blood flow associated with acute hypoxia. Here, the
possible correlation between tumor vessel immaturity, vessel functionality and
T2*w GRE signal fluctuations was investigated. Intramuscularly implanted FSa II
fibrosarcoma-bearing mice were imaged at 4.7 T. Maps of spontaneous fluctuations
of MR signal intensity in tumor tissue during air breathing were obtained using
a T2*w GRE sequence. This same sequence was also employed during air-5% CO2
breathing (hypercapnia) and carbogen breathing (hypercapnic hyperoxia) to obtain
parametric maps representing vessel maturation and vessel function,
respectively. Vascular density, vessel maturation and vessel perfusion were also
assessed histologically by using CD31 labeling, alpha-smooth muscle actin
immunoreactivity and Hoechst 33242 labeling, respectively. About 50% of the
tumor fluctuations occurred in functional tumor regions (responsive to carbogen)
and 80% occurred in tumor regions with immature vessels (lack of response to
hypercapnia). The proportion of hypercapnia-responsive voxels were found to be
twice as great in fluctuating than in non-fluctuating tumor areas (P: 0.22 vs
0.13). Similarly, the proportion of functional voxels was somewhat greater in
fluctuating tumor areas (P: 0.54 vs 0.43). The mean values of MR signal changes
during hypercapnia (VD) and during carbogen breathing (VF) (significant voxels
only) were also larger in fluctuating than in non-fluctuating tumor areas (P <
0.05). This study demonstrated that adequate vessel functionality and advanced
vessel maturation could explain at least in part the occurrence of spontaneous
T2*w GRE signal fluctuations. Functionality and maturation are not required for
signal fluctuations, however, because a large fraction of fluctuations could
still occur in non-perfused and/or immature vessels. 2006 John Wiley & Sons,
Ltd.

PMID: 16411170 [PubMed - in process]