Summary The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using 31p magnetic resonance spectroscopy (MRS), fluorescence microscopy and twodimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (Pi/NTP) ratio increased rapidly as mean intervascular distances increased from 100 gm to 300 ,um. Two morphometric parameters -the percentage of intervascular distances larger than 200 gm (ivd200) and the non-perfused area fraction at a distance larger than 100 ,um from a nearest perfused vessel (areal0o), -were deduced from these experiments and related to the P/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the Pi/NTP ratio increased linearly with the percentage of ivd200 and the area100.Keywords: 31p magnetic resonance spectroscopy; fluorescence microscopy; tumour bioenergetic status; vascular morphology Phosphorus magnetic resonance spectroscopy (31P-MRS) studies of the bioenergetic status of tumours have been compared directly with tumour tissue po2 (Vaupel et al, 1989a) and with several physiological parameters that affect pO2 in tumour tissue, such as the intravascular concentration of oxyhaemoglobin (Rofstad et al, 1988) and tumour blood perfusion (Evelhoch et al, 1986). 31P-MRS has been demonstrated to be sensitive to tumour size (Okunieff et al, 1986;Wendland et al, 1992), with an increase in tumour size being supposed to have a negative influence on perfusion-and diffusion-limited oxygen delivery and nutrient delivery (Vaupel, 1996). The global bioenergetic status of a tumour, expressed as the P/NTP ratio, depends on the balance between the oxygen and nutrient supply, and the consumption rates of the tumour cells, which is related to the type of energy metabolism. This balance between supply and consumption determines the critical diffusion distances for oxygen and nutrients in tumour tissue. The total oxygen supply and nutrient supply depends on the tumour microcirculation and on the diffusion geometry.The purpose of this study was to investigate the existence of a possible relationship between the global bioenergetic status and the diffusion geometry of human glioma xenografts in nude mice. A two-dimensional morphometric analysis of the perfused vascular architecture of complete transverse tumour sections was performed. Morphometric parameters, such as the percentage of large intervascular distances and the fraction of non-perfused areas in a tumour section area, are related to the diffusion-limited

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