Quantitative fluorescence tomography using a trimodality system: in vivo validation

Abstract

A fully integrated trimodality fluorescence, diffuse optical, and x-ray computed tomography (FT/DOT/XCT) system for small animal imaging is reported in this work. The main purpose of this system is to obtain quantitatively accurate fluorescence concentration images using a multimodality approach. XCT offers anatomical information, while DOT provides the necessary background optical property map to improve FT image accuracy. The quantitative accuracy of this trimodality system is demonstrated in vivo. In particular, we show that a 2-mm-diam fluorescence inclusion located 8 mm deep in a nude mouse can only be localized when functional a priori information from DOT is available. However, the error in the recovered fluorophore concentration is nearly 87%. On the other hand, the fluorophore concentration can be accurately recovered within 2% error when both DOT functional and XCT structural a priori information are utilized together to guide and constrain the FT reconstruction algorithm.

Figure 1

(a) Schematic diagram of the FT/DOT/XCT system. The components seen in the schematic diagram are: 1. the sample holder, 2. x-ray source, 3. x-ray detector, 4. CCD camera, 5. filter wheel, 6. lens, 7. phantom, 8. fiber optic collimator, 9. optical fibers, and 10. fiber optic switch. (b) The picture of the system from the front view showing the FT/DOT components.

Figure 2

XCT images for (a) the first and (b) second cases. The positions of the ICG inclusions and the carbon rods are indicated by yellow arrows. (Color online only.)

Figure 3

The reconstructed ICG concentration maps for the subcutaneously implanted inclusion (first case). (a) The inclusion can be identified from the reconstructed ICG map, even without any a priori information. (b) On the other hand, the recovered ICG concentration is more accurate when DOT functional a priori information is utilized. (c) Finally, when both XCT structural and DOT functional a priori information is used to guide the FT reconstruction together, the ICG concentration is recovered within 2% error, 510 nM.

Figure 4

The reconstructed ICG concentration maps for the inclusion deeply embedded inside of the mouse (second case). (a) The inclusion cannot be located at all without any a priori information. (b) ICG inclusion, on the other hand, can be localized when DOT functional a priori information is provided. The recovered ICG concentration, however, is still underestimated by 80%, 62 nM. (c) When both DOT functional and XCT structural a priori information is used, the ICG concentration is recovered within 3% error, 487 nM.