MAGNETIC-RESONANCE-IMAGING OF HUMAN-MELANOMA XENOGRAFTS IN-VIVO - PROTON SPIN-LATTICE AND SPIN-SPIN RELAXATION-TIMES VERSUS FRACTIONAL TUMOR WATER-CONTENT AND FRACTION OF NECROTIC TUMOR-TISSUE

Proton nuclear magnetic resonance (H-1-nmr) imaging is used routinely in clinical oncology to provide macroscopic anatomical information, wh ereas its potential to provide physiological information about tumours is not well explored. To evaluate the potential usefulness of H-1-nmr imaging in the prediction of tumour treatment resistance caused by un favourable microenvironmental conditions, possible correlations betwee n proton spin-lattice and spin-spin relaxation times (T-1 and T-2) and physiological parameters of the tumour microenvironment were investig ated. Tumours from six human melanoma xenograft lines were included in the study. H-1-nmr imaging was performed at 1.5 T using spin-echo pul se sequences. T-1- and T-2-distributions were generated from the image s. Fractional tumour water content and the fraction of necrotic tumour tissue were measured immediately after H-1-nmr imaging. Significant c orrelations across tumour lines were found for T-1 and T-2 versus frac tional tumour water content (p < 0.001) as well as for T-1 and T-2 ver sus fraction of necrotic tumour tissue (P < 0.05). Tumours with high f ractional water contents had high values of T-1 and T-2, probably caus ed by free water in the tumour interstitium. Fractional water content is correlated to interstitial fluid pressure in tumours, high intersti tial fluid pressure being indicative of high vascular resistance. Tumo urs with high fractional water contents are thus expected to show regi ons with radiobiologically hypoxic cells as well as poor intravascular and interstitial transport of many therapeutic agents. T-1 and T-2 de creased with increasing fraction of necrotic tumour tissue, perhaps be cause complexed paramagnetic ions were released during development of necrosis. Viable tumour cells adjacent to necrotic regions are usually chronically hypoxic. Tumours with high fractions of necrotic tissue a re thus expected to contain significant proportions of radiobiological ly hypoxic cells. Consequently, quantitative H-1-nmr imaging has the p otential to be developed as an efficient clinical tool in prediction o f tumour treatment resistance caused by hypoxia and/or transport barri ers for therapeutic agents. However, much work remains to be done befo re this potential can be adequately evaluated. One problem is that hig h fractional tumour water contents result in longer T-1 and T-2 wherea s high fractions of necrotic tumour tissue result in shorter T-1 and T -2; i.e. the two parameters which are indicative of treatment resistan ce contribute in opposite directions. Another problem is that the corr elations for T-1 and T-2 versus fraction of necrotic tumour tissue are not particularly strong.