Optimizing ultrasound molecular imaging of secreted frizzled related protein 2 expression in angiosarcoma
Fig 3
Time-Intensity Curves (TICs) generated from a representative animal that received both SFRP2-targeted, and IgY-targeted control contrast.
(A) SFRP2-targeted contrast: solid blue line represents intensity within the tumor ROI, dotted black line represents intensity within a non-tumor ROI, red filled circles represent the difference between the tumor and non-tumor ROI intensities, which we term ‘free-flowing-corrected’ TIC (ffc-TIC). (B) IgY-targeted contrast: solid green line represents intensity within the tumor ROI, dotted black line represents intensity within a non-tumor ROI, purple open circles represent the difference between the tumor and non- tumor ROI intensities, which we term ‘free-flowing-corrected’ TIC (ffc-TIC). (C) The wash out of contrast from tumor ROI was modeled by one-phase exponential decay for IgY-targeted contrast (raw data, open green circles; green line, best-fit model), and by a plateau followed by one-phase exponential decay for SFRP2-targeted contrast (raw data, solid blue circles; blue line, best-fit model). (D) The difference between the models depicted in panel (C) was plotted with open black triangles. Note the maxima between 6–10 minutes. (E) The ffc-TICs for SFRP2, and IgY-targeted contrast were fitted to curves. A one-phase association model (grey line) fit the wash in portion of the ffc-TIC for SFRP2-targeted contrast (red filled circles), and for IgY-targeted contrast (open purple circles). The wash out of SFRP2-targeted ffc-TIC was best fit with a linear regression model (blue line), while the wash out of IgY-targeted ffc-TIC was best fit with a one-phase exponential decay model (green line). (F) The best-fit model for the IgY-targeted ffc-TIC was subtracted from the best-fit model for SFRP2-targeted ffc-TIC, and was plotted (red filled circles with red line). This produced a TIC representing the signal intensity within the tumor ROI that could be attributed to binding of contrast specifically mediated by the SFRP2 antibodies used to formulate the SFRP2-targeted contrast. N = 5 animals.