Non-invasive assessment for intratumoural distribution of interstitial fluid flow

Abstract

Interstitial fluid plays a vital role in drug delivery and tumour treatment. However, few non-invasive measurement methods are available for measuring low-velocity biological fluid flow. Therefore, this study aimed to develop a novel technology called interstitial flow velocity-MRI. The interstitial flow velocity-MRI sequence consists of a dual inversion recovery preparation and an improved stimulated echo sequence (ISTE) combined with phase-contrast MRI. A homemade flow phantom was used to assess the feasibility and sensitivity of interstitial flow velocity-MRI. In addition, xenografts of female BALB/c mouse models of 4T1 breast cancer administered losartan (40 mg/kg) or saline (n = 6) were subjected to imaging on a 7.0 T scanner to assess the in vivo interstitial fluid flow velocity. The results showed a significant correlation (P < 0.001) between the theoretical velocities and velocities measured using the flow phantom. Interstitial flow velocity-MRI could detect a velocity as low as 10.21 ± 2.65 μm/s with a spatial resolution of 0.313 mm. The losartan group had a lower mean interstitial fluid velocity than the control group (85 ± 16 vs 113 ± 24 μm/s). In addition, compared to the saline treatment, losartan treatment reduced the proportion of collagen fibres by 10% and 12% in the Masson and Sirius red staining groups, respectively. Interstitial flow velocity-MRI has the potential to determine interstitial fluid flow velocity non-invasively and exhibits an intuitive velocity map.

Keywords

• Interstitial fluid flow
• Interstitial flow velocity-MRI
• Losartan
• Slow flows
• Tumour microenvironment