Abstract
The increased interstitial fluid pressure (IFP) from vasogenic edema, which results from a leaky blood-tumor-barrier (BTB), creates a barrier for transvascular drug delivery, particularly larger molecules that are unable to diffuse across and must resort to bulk fluid flow. We have previously used dynamic contrast enhanced-computed tomography (DCE-CT) to quantitatively evaluate the blood-brain-barrier (BBB) response in normal brain - and have shown that focused ultrasound (FUS) and microbubble (MB) treatment in a rat brain demonstrates a 3-4 times transient increase at our optimized parameters. The purpose of this study was to quantitatively evaluate the BTB response following FUS and MB treatment in rat glioma, in the context of improving drug delivery to brain tumors.
Highlights
Background/introduction The increased interstitial fluid pressure (IFP) from vasogenic edema, which results from a leaky bloodtumor-barrier (BTB), creates a barrier for transvascular drug delivery, larger molecules that are unable to diffuse across and must resort to bulk fluid flow
dynamic contrast enhanced-computed tomography (DCE-CT) (80 kVp, 250 mA, axial slice thickness = 1.25 mm) was performed using a two phase protocol: 1st phase consisting of continuous 0.5 s rotations for 30 s, and a 2nd phase of 0.5 s rotations at 14.5 s intervals for 150s. 2.5 ml/kg of iodinated contrast agent was injected over 5 seconds simultaneous to the start of each DCE-CT scan
Proprietary CT Perfusion software was used to compute permeability surface area product (PS), cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps using a standard small molecule contrast agent (Isovue ~ 760 Da) that is able to diffuse across the BTB
Summary
Background/introduction The increased interstitial fluid pressure (IFP) from vasogenic edema, which results from a leaky bloodtumor-barrier (BTB), creates a barrier for transvascular drug delivery, larger molecules that are unable to diffuse across and must resort to bulk fluid flow. We have previously used dynamic contrast enhanced-computed tomography (DCE-CT) to quantitatively evaluate the blood-brain-barrier (BBB) response in normal brain - and have shown that focused ultrasound (FUS) and microbubble (MB) treatment in a rat brain demonstrates a 3-4 times transient increase at our optimized parameters. The purpose of this study was to quantitatively evaluate the BTB response following FUS and MB treatment in rat glioma, in the context of improving drug delivery to brain tumors
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