High Microvascular Blood Volume Is Associated with High Glucose Uptake and Tumor Angiogenesis in Human Gliomas

High Microvascular Blood Volume Is Associated with High Glucose Uptake and Tumor Angiogenesis in Human Gliomas1

MGH-NMR Center [H. J. A., F. S. P., D. N. K., J. W. B., S. D. P., B. R. R.] and Departments of Radiology [ J. W. B., B. R. R.], Neurology [ D. N. K.], Pathology/Neuropathology [D. W. H.], and Neurosurgery [F. H. H.], Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts 02114; Department of Radiology, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland [ H. J. A.]; Department of Radiation Medicine, New York Medical College, Valhalla, New York 10595 [ F. S. P.]; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts 02139 [ S. D. P.]; Department of Nuclear Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 [ S. D. P.]

Abstract

The purpose of this investigation was to elucidate the association between microvascular blood volume and glucose uptake and to link these measures with tumor angiogenesis. We demonstrate a regionally specific correlation between tumor relative microvascular blood volume (CBV), determined in vivo with functional magnetic resonance imaging techniques, and tumor glucose uptake determined with fluorodeoxyglucose positron emission tomography. Regions of maximum glucose uptake were well matched with maximum CBV across all patients (n = 21; r = 0.572; P = 0.023). High-grade gliomas showed significantly elevated CBV and glucose uptake compared with low-grade gliomas, (P = 0.009 and 0.008, respectively). Correlations between CBV and glucose uptake were then determined on a voxel-by-voxel basis within each patient’s glioma. Correlation indices varied widely, but in 16 of 21 cases of human glioma, CBV and glucose uptake were correlated (r > 0.150). These measures were well correlated in all cases when comparing healthy brain tissue in these same patients. Tumor vascularity, as determined immunohistochemically and morphometrically on clinical samples, revealed statistically significant relationships with functional imaging characteristics in vivo. Regional heterogeneities in glucose uptake were well matched with functional magnetic resonance imaging CBV maps. Our findings support the concept that there is an association of microvascular density and tumor energy metabolism in most human gliomas. In addition, the findings are likely to have important clinical applications in the initial evaluation, treatment, and longitudinal monitoring of patients with malignant gliomas.

Footnotes

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↵1 This work was supported in part by the Academy of Finland (to H. J. A.), the Cancer Organizations of Finland (to H. J. A.), the Cultural Foundation of Finland (to H. J. A.), Vuorisalo Foundation, Helsinki, Finland (to H. J. A.), Paulo Foundation, Helsinki, Finland (to H. J. A.), Ella and George Ehrnrooth Foundation, Helsinki, Finland (to H. J. A.), Helsinki University Central Hospital (to H. J. A.), NIH Fogarthy International Center Grant 1 F05 TW04520 (to H. J. A.), and NIH Grants RO1-CA40303, RO1-HL39810, and POI-CA48729. This research was conducted during the tenure of an established investigator award to J. W. B. from the American Heart Association.
↵2 To whom requests for reprints should be addressed, at MGH-NMR Center, 2nd Floor, Building 149, 13th Street, Charlestown, MA 02129. Phone: (617) 726-5122; Fax: (617) 726-7422; E-mail: bruce{at}nmr.mgh.harvard.edu
↵3 The abbreviations used are: PET, positron emission tomography; FDG, fluorodeoxyglucose; fMRI, functional magnetic resonance imaging; CBV, cerebral blood volume; TR, repetition time; TE, echo time; ROI, region(s) of interest; CBF, cerebral blood flow; BBB, blood-brain barrier.
- Accepted March 23, 2000.
- Received March 23, 1999.
- Revision received January 26, 2000.