Optimizing ultrasound molecular imaging of secreted frizzled related protein 2 expression in angiosarcoma
Fig 2
3-dimensional molecular imaging protocols estimated video intensity of free flowing contrast, with and without destruction of microbubbles.
Prior to injection of targeted contrast agent, anatomical features were recorded with a B-mode scan (black arrow). The first contrast-specific, Cadence™ contrast pulse sequencing scan was performed in the absence of contrast (blue line capped with open circle) to establish the average video pixel intensity (VI) of ROIs at baseline. (A) Time-intensity curves (TICs). A ‘non-destructive imaging scheme’ captured multiple Cadence™ mode scans during the first 2 minutes post-injection to capture wash-in of the contrast bolus, and then every two minutes between 2 to 20 minutes post-injection. Average video pixel intensities from a representative study were plotted, showing total signal from tumor ROIs (black line) and from non-tumor ROIs (dotted blue line). The TIC from non-tumor ROIs was used later to approximate the signal contributed by freely flowing contrast. (B) An image—destroy—image’ scheme was used to differentiate targeted contrast bound within tumor endothelium from targeted contrast flowing freely in the vasculature. A Cadence™ mode scan was captured at a pre-determined time (10 minutes, pre-destruction scan, blue arrow) to determine the average video pixel intensity in the tumor ROI. This was followed immediately by a high mechanical index (D-Color) scan to destroy all bound and freely flowing contrast within the tumor ROI (red arrow, destructive scan). A pause of 60 seconds allowed freely flowing contrast to re-enter the tumor vasculature, and a final Cadence™ mode scan was captured (12 minutes, post-destruction scan, blue arrow) to estimate the average VI contributed by freely flowing contrast. The average video pixel intensity contributed by contrast bound to endothelium was calculated by subtracting the average VI of the post-destruction scan from the average VI of the pre-destruction scan. Average video pixel intensity for all scans was reported after subtracting the average video pixel intensity of the baseline scans.