Neoplasia. 2003 Jul-Aug;5(4):330-8 doi: NO_DOI.

Functional response of tumor vasculature to PaCO2: determination of total and microvascular blood volume by MRI

Packard SD, Mandeville JB, Ichikawa T, Ikeda K, Terada K, Niloff S, Chiocca EA, Rosen BR, Marota JJ.


In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered P(a)CO(2). Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total +/- CBV increased by 0.6 +/- 0.1%/mm Hg CO(2) whereas normal striatum increased by 1.5 +/- 0.2%/mm Hg CO(2), (P <.0001 group="" t-test="" reactivity="" of="" microvascular="" blood="" volume="" was="" also="" significantly="" blunted.="" in="" contrast="" hypocarbia="" decreased="" both="" total="" and="" volumes="" more="" glioma="" than="" normal="" striatum.="" these="" results="" indicate="" that="" cerebral="" vessels="" derived="" by="" tumor-directed="" angiogenesis="" do="" retain="" to="" co="" furthermore="" reduced="" tumor="" a="" single="" physiological="" perturbation="" such="" as="" hypercarbia="" should="" not="" be="" construed="" generalized="" reduction="" functional="" activity="" the="" vascular="" bed.="">

PMID: 14511404