Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.

BACKGROUND: The aim of our study was to compare 90Y dosimetry obtained from PET/MRI versus PET/CT post-therapy imaging among patients with primary or metastatic hepatic tumors. First, a water-filled Jaszczak phantom containing fillable sphere with 90Y-chloride was acquired on both the PET/CT and PET/MRI systems, in order to check the cross-calibration of the modalities. Following selective internal radiation therapy (SIRT) with 90Y microspheres, 32 patients were imaged on a PET/CT system, immediately followed by a PET/MRI study. Reconstructed images were transferred to a common platform and used to calculate 90Y dosimetry. A Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between the dosimetry values.
RESULTS: The phantom study showed that both modalities were calibrated with less than 1% error. The mean liver doses for the 32 subjects calculated from PET/CT and PET/MRI were 51.6 ± 24.7 Gy and 46.5 ± 22.7 Gy, respectively, with a mean difference of 5.1 ± 5.0 Gy. The repeatability coefficient was 9.0 (18.5% of the mean). The Spearman rank correlation coefficient was very high, ρ = 0.97. Although the maximum dose to the liver can be significantly different (up to 40%), mean liver doses from each modalities were relatively close, with a difference of 18.5% or less.
CONCLUSIONS: The two main contributors to the difference in 90Y dosimetry calculations using PET/CT versus PET/MRI can be attributed to the differences in regions of interest (ROIs) and differences attributed to attenuation correction. Due to the superior soft-tissue contrast of MRI, liver contours are usually better seen than in CT images. However, PET/CT provides better quantification of PET images, due to better attenuation correction. In spite of these differences, our results demonstrate that the dosimetry values obtained from PET/MRI and PET/CT in post-therapy 90Y studies were similar.

BACKGROUND: A major toxicity concern in radioembolization therapy of hepatic malignancies is radiation-induced pneumonitis and sclerosis due to hepatopulmonary shunting of 90Y microspheres. Currently, 99mTc macroaggregated albumin (99mTc-MAA) imaging is used to estimate the lung shunt fraction (LSF) prior to treatment. The aim of this study was to evaluate the accuracy/precision of LSF estimated from 99mTc planar and SPECT/CT phantom imaging, and within this context, to compare the corresponding LSF and lung-absorbed dose values from 99mTc-MAA patient studies. Additionally, LSFs from pre- and post-therapy imaging were compared.
RESULTS: A liver/lung torso phantom filled with 99mTc to achieve three lung shunt values was scanned by planar and SPECT/CT imaging with repeat acquisitions to assess accuracy and precision. To facilitate processing of patient data, a workflow that relies on SPECT and CT-based auto-contouring to define liver and lung volumes for the LSF calculation was implemented. Planar imaging-based LSF estimates for 40 patients, obtained from their medical records, were retrospectively compared with SPECT/CT imaging-based calculations with attenuation and scatter correction. Additionally, in a subset of 20 patients, the pre-therapy estimates were compared with 90Y PET/CT-based measurements. In the phantom study, improved accuracy in LSF estimation was achieved using SPECT/CT with attenuation and scatter correction (within 13% of the true value) compared with planar imaging (up to 44% overestimation). The results in patients showed a similar trend with planar imaging significantly overestimating LSF compared to SPECT/CT. There was no correlation between lung shunt estimates and the delay between 99mTc-MAA administration and scanning, but off-target extra hepatic uptake tended to be more likely in patients with a longer delay. The mean lung absorbed dose predictions for the 28 patients who underwent therapy was 9.3 Gy (range 1.3-29.4) for planar imaging and 3.2 Gy (range 0.4-13.4) for SPECT/CT. For the patients with post-therapy imaging, the mean LSF from 90Y PET/CT was 1.0%, (range 0.3-2.8). This value was not significantly different from the mean LSF estimate from 99mTc-MAA SPECT/CT (mean 1.0%, range 0.4-1.6; p = 0.968), but was significantly lower than the mean LSF estimate based on planar imaging (mean 4.1%, range 1.2-15.0; p = 0.0002).
CONCLUSIONS: The improved accuracy demonstrated by the phantom study, agreement with 90Y PET/CT in patient studies, and the practicality of using auto-contouring for liver/lung definition suggests that 99mTc-MAA SPECT/CT with scatter and attenuation corrections should be used for lung shunt estimation prior to radioembolization.

For phantom studies involving (90)Y PET/CT, homogeneous solutions of (90)Y, for example, (90)Y citrate, are commonly used. However, the microsphere biodistribution of a postradioembolization liver is never homogeneous; therefore, such phantoms are physiologically unrealistic for simulating clinical scenarios. The aim of this work was to develop a safe and practical phantom capable of simulating the heterogeneous microsphere biodistribution of a postradioembolization liver.
METHODS: Gelatin (5%) was used to suspend (90)Y resin microspheres, poured into plastic containers to simulate a liver with 2 tumors. Microspheres were added while the gelatin was maintained in a liquid state on a hot plate and continuously stirred with magnetic stir bars. The liquid microsphere mixture was then rapidly cooled in an ice bath while being stirred, resulting in a heterogeneous suspension of microspheres. The completed phantom was serially scanned by (90)Y PET/CT over 2 wk.
RESULTS: All scans demonstrated a heterogeneous microsphere distribution throughout the liver and tumor inserts. Serendipitously, magnetic stir bars left inside the phantom produced CT artifacts similar to those caused by embolization coils, whereas pockets of air trapped within the gelatin during its preparation mimicked gas within hollow viscus. The microspheres and tumor inserts remained fixed and suspended within the gelatin, with no evidence of breakdown or leakage.
CONCLUSIONS: A gelatin phantom realistically simulating the physiologic microsphere biodistribution of a postradioembolization liver is feasible to construct in a radiopharmacy.