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Johnson, S. P.

Publications and source records attributed to Johnson, S. P..

2 recordsLinked to original sources
bioRxiv2017

Investigating low-velocity fluid flow in tumours using convection-MRI

Several distinct fluid flow phenemena occur in solid tumours, including intravascular blood flow and interstitial convection. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we have developed a novel magnetic resonance imaging (MRI) technique named convection-MRI. It uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extra-vascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations and tumor xenograft models to investigate the technical feasibility of convection-MRI. We report a good correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma and show that convection-MRI can provide insights into the growth and response to vascular-targeting therapy in colorectal cancers.

biophysics↗
bioRxiv2017

Development of noninvasive biomarkers of response to proteasome inhibitor therapy (ixazomib) by imaging disrupted protein homeostasis in mouse models of solid tumors

With clinically-approved proteasome inhibitors now a standard of care for multiple myeloma, and increasing interest in their use in solid tumors, methods for monitoring therapeutic response in vivo are critically required. Here, we show that tumor protein homeostasis can be noninvasively monitored, using chemical exchange (CEST) magnetic resonance imaging (MRI) as a surrogate marker for proteasome inhibition, alongside diffusion MRI and relaxometry. We show that the in vivo CEST signal associated with amides and amines increases in proportion to proteasome inhibitor dose (ixazomib) and the magnitude of therapeutic effect in colorectal cancer xenografts. Moreover, we show that SW1222 and LS174T human colorectal cancer cell lines demonstrate differing sensitivities to ixazomib, which was reflected in our MRI measurements. We also found evidence of a mild stimulation in tumor growth at low ixazomib doses. Our results therefore identify CEST MRI as a promising method for safely and noninvasively monitoring changes in tumor protein homeostasis.

biophysics↗