A simple method for measuring interstitial fluid pressure in cancer tissues

Abstract

A novel procedure using a polyurethane transducer-tipped catheter (Millar) is described that allows reliable measurement of interstitial fluid pressure (IFP) in cancer tissues. Before and after each use, the transducer is calibrated at 37 degrees C by a water column. After calibration, the transducer is passed through the lumen of a surgical needle. The sensor is kept in the lumen of the needle during penetration into the tumor. The sensor tip is then introduced into the center core of the tumor as the needle sleeve is withdrawn from the tumor surface. Our new technique is simple and provides IFPs equal to those provided by the well-established, wick-in-needle technique. Using our new technique, we compared IFP in skin melanoma grafts in NG2 knockout and wild-type mice. Knocking out NG2 proteoglycan on vasculogenic and angiogenic pericytes reduced interstitial fluid pressure in melanoma from +4.9 cm H2O to -0.4 cm H2O (P=0.0054 Mann-Whitney U test).

Fig. 1

Interstitial fluid pressure measurement with ultraminiature pressure transducer. (A) The ultraminiature transducer (arrow) is introduced percutaneously 1 mm through the tumor capsule into the superficial tumor in a protective metal guide (18-gauge needle) (arrowhead). (B) The metal guide is withdrawn slowly, while the sensor is introduced into the center of the tumor. The location of the center of the tumor is estimated by dividing the caliper-measured diameter of tumor in half. The transducer can be marked for millimeter gradation using standard fine point pens (not shown in this picture). (C) Handling of the needle guide and transducer is very easy during microsurgical procedures on mice. Scale bar = 600 μm.

Fig. 2

Calibration of the miniature transducer. The miniature transducer is calibrated in distilled water column at 37°C (A). Calibration curves both before (pretest) and after (posttest) in vivo measurements show a linear correlation between the depth of water column (pressure in cm H₂O) and transducer output (mV) (B).

Fig. 3

Targeting NG2 proteoglycan on neovascular pericytes reduces interstitial hypertension in skin melanoma in mice. IFP measurements were performed 2 weeks following subcutaneous tumor grafting. Intrinsic (genetic) inhibition of NG2 proteoglycan decreases IFP in B16F1 melanoma grafts in NG2 knockout mice (average core IFP of −0.4 cm H₂O) compared to B16F1 melanoma grafts in wild type controls[C0](average core IFP of +4.9 cm H₂O) (n = 24, P = 0.0054 Mann–Whitney U test).