Precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model

Abstract

Purpose: To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry.

Materials and methods: A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland-Altman analysis.

Results: A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r² > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r² = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10^-12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland-Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively.

Conclusion: The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose-response relationship, which could ultimately improve future patient outcomes.

Keywords: CT; Dosimetry; Microsphere; PET; Radioembolization; Radiopacity; Yttrium-90.

Fig. 1

a Image of the calibration phantom overlaid with physical dimensions. b Axial CT slice [− 100 to 200 HU] of the calibration phantom with segmented structures for a background region (magenta) and three microsphere concentrations: 0.5 mg/mL (green), 5.0 mg/mL (red), and 25.0 mg/mL (blue). c Segmented structures in the calibration phantom

Fig. 2

Baseline unenhanced axial CT slice [− 100 to 200 HU] of R03 following the administration of Eye90 showing four structures: the rabbit’s body $B$ (yellow), the liver volume $L$ (blue), the liver extended by an isotropic 1 cm margin $L_{\text{shell}}$ (red), and the non-embolized, homogeneous background region $L_{\text{bkg}}$ (magenta)

Fig. 3

The average CT voxel value within post structures as a function of post diameter for the three microsphere concentrations within the CT calibration phantom: 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. Error bars represent the standard deviation of the voxel values within a post

Fig. 4

A calibration curve derived from the analysis of the calibration phantom. The coefficient of determination is r² ≥ 0.999. Voxel values were extracted for the 15 mm-diameter posts only

Fig. 5

a Calibration curves derived for all post sizes within the calibration phantom. b Calibration curve slope as a function of post diameter with error bars representing 95% confidence intervals

Fig. 6

a The microsphere mass in the 2 mm-diameter post with a microsphere concentration of 25.0 mg/mL as a function of contour shell thickness. The nominal mass of Eye90 within the contour is represented by the dashed horizontal line. b Axial CT slice [− 50 to 400 HU] of the 2 mm-diameter post with a microsphere concentration of 25.0 mg/mL. The red contours represent extended shell thicknesses

Fig. 7

Sagittal slices of the PET-based activity distribution $A_{\text{PET}}$ a before filtering with a 4 mm FWHM Gaussian kernel, and b after filtering with a 4 mm FWHM Gaussian kernel. The red contour represents the liver volume $L$ and the blue contour represents the circular ROI where the standard deviation of ⁹⁰Y activity concentration values was measured. The concentration values are displayed with a range of 0–1.0 MBq/mL

Fig. 8

a 3D surface plot through the central voxel in the CT dose-voxel kernel DVK_CT. b 2D cross section through the central voxel in the CT dose-voxel kernel DVK_CT. c 3D surface plot through the central voxel in the PET dose-voxel kernel DVK_PET. d 2D cross section through the central voxel in the PET dose-voxel kernel DVK_PET. The maximum value in all vertical axes and colour bars corresponds to the maximum value of DVK_CT

Fig. 9

a–c Axial, sagittal, and coronal views of the CT-based dose distribution ${\text{DD}}_{\text{CT}}$ in R05 overlaid on an axial CT [− 100 to 200 HU]. d–f Axial, sagittal, and coronal views of the PET-based dose distribution ${\text{DD}}_{\text{PET}}$ in R05 overlaid on an axial CT [− 100 to 200 HU]

Fig. 10

a–c Axial, sagittal, and coronal views of the CT-based dose distribution ${\text{DD}}_{\text{CT}}$ in R06 overlaid on an axial CT [-100 to 200 HU]. d–f Axial, sagittal, and coronal views of the PET-based dose distribution ${\text{DD}}_{\text{PET}}$ in R06 overlaid on an axial CT [− 100 to 200 HU]

Fig. 11

a Linear regression analysis with 95% confidence intervals (dashed) and identity line (dotted) for the mean dose $D_{\mu }$ in the CT-based dose distribution ${\text{DD}}_{\text{CT}}$ and in the PET-based dose distribution ${\text{DD}}_{\text{PET}}$. b Bland–Altman analysis with 95% confidence intervals (dashed)

Fig. 12

Box-and-whisker plot for the mean dose $D_{\mu }$ across all rabbits extracted from the CT-based dose distribution ${\text{DD}}_{\text{CT}}$, the PET-based dose distribution ${\text{DD}}_{\text{PET}}$, and ${\text{DD}}_{\text{MRD}}$. The red line represents the median value, the blue box contains data between the 25th and 75th percentiles, and the black whiskers extend to the most extreme data points

Fig. 13

Cumulative dose volume histograms (cDVHs) for the liver volumes $L$ and $L_{\text{shell}}$ across all rabbits