Evaluation of quantitative accuracy in 4D DCE-bCT: Insights from a perfusion phantom study

Four-dimensional dynamic contrast-enhanced breast CT (4D DCE-bCT) provides submillimeter spatial resolution and temporal sampling within seconds, offering potential for improved perfusion assessment in breast cancer. Its quantitative accuracy, however, must be validated.

To evaluate the accuracy of dynamic iodine concentration quantification in 4D DCE-bCT using a perfusion phantom with in-line optical spectroscopy and ultraviolet-visible (UV/VIS) spectrophotometry as reference standards.

A dynamic flow phantom with a 3 mm internal diameter was used to approximate tumor-feeding vessels. Potassium iodide (KI) contrast was introduced using block-pulse injections at 1, 3, and 5 mg I/mL and a gradual inflow-outflow protocol to reproduce bolus passage. In-line optical spectroscopy and UV/VIS spectrophotometry provided reference measurements. Dynamic bCT acquisitions were performed using a previously developed sparse-view protocol. A static pre-contrast scan was reconstructed with the iterative maximum-likelihood polychromatic algorithm for CT (IMPACT), and post-contrast dynamic scans were reconstructed using the prior image constrained compressed sensing (PICCS) algorithm. Acquisitions were performed at 65 kV with 0.25 mm Cu filtration, 80 mA for the pre-contrast scan (300 projections over 10 s) and 32 mA for the post-contrast scans (444 projections per 100 s), using a 5 ms pulse width. Projection data were corrected for scatter and motion before reconstruction, and the static prior was then subtracted from post-contrast volumes. Object-size effects were evaluated using the 3 mm tube and 5, 10, 15, and 20 mm hollow spheres filled with non-flowing iodine at 1, 3, and 5 mg I/mL. The tube interior was segmented using thresholding and morphological cleanup, while spherical phantoms were segmented by identifying the sphere center and extracting all enclosed voxels. Voxel values were converted to iodine concentration using a pre-determined calibration curve, and agreement with reference standards was evaluated using peak concentrations and time-concentration profiles, with errors reported as absolute and relative differences.

In dynamic block-pulse experiments, peak iodine concentrations measured by 4D DCE-bCT were systematically underestimated relative to ground truth, with relative errors of approximately 12% to 39%. In gradual inflow-outflow experiments, the peak iodine concentration derived from 4D DCE-bCT was 5.24 ± 0.61 mg I/mL, whereas optical ground truth measured 5.17 mg I/mL. Static experiments demonstrated an average underestimation of 0.23 ± 0.14 mg I/mL across target sizes and concentrations and no relationship between iodine estimation and target size.

4D DCE-bCT enabled acquisition of time-varying iodine concentration profiles in a 3 mm tube phantom. Gradual changes were captured more accurately compared to rapid changes, consistent with temporal averaging. These results demonstrate the feasibility of dynamic iodine imaging with 4D DCE-bCT while highlighting current limitations and motivating further evaluation in anatomically realistic phantoms and pilot clinical studies.