To the best of our knowledge, this is the first comparison of PET/CT and PET/MRI imaging and dosimetry in 90Y post-treatment studies [3]. In mutual comparison between PET/CT and PET/MRI, each modality has advantages and disadvantages. The advantages of PET/CT modality is better attenuation correction and thus better quantification, plus faster acquisition time. In PET/CT, the time for CT acquisition is measured in seconds and total acquisition time is determined by the PET component. In PET/MRI, it is the other way around. MRI determines acquisition time, which is mostly determined by the number of MRI sequences. However, the advantages of PET/MRI are lower radiation dose and better soft-tissue contrast, which is essential for accurately delineating healthy liver tissue versus tumors during analysis [24]. Also, due to their different data acquisition approaches, i.e., sequential for PET/CT vs. simultaneous for PET/MRI, PET/MRI offers the opportunity to directly image respiration liver motion during the PET acquisition and correct for it during the PET reconstruction [25]. In addition, high spatial resolution MR images, which offer high soft-tissue contrast, could be used in partial volume (PV) correction of the lower resolution PET images [26, 27].
In our study, PET/MRI led to underestimation of the mean liver dose values by less than 10% on average, when compared to PET/CT. In some cases, PET/MRI values were almost the same or even slightly higher than PET/CT values. In our previous work [28], in which we compared MR-based and CT-based attenuation corrections on the same subjects, SUVmean and SUVmax values obtained from PET/CT were slightly higher in values than the corresponding values obtained from PET/MRI. It seems that the same trend is present in comparison of dosimetry values in 90Y post-therapy studies (Fig. 3). In both cases, the reason for the variation in these values lies in the difference of attenuation corrections applied. However, in this comparison, additional source of difference is also attributed to creation of ROIs from CT and MRI anatomic images, which were used for dosimetry calculations. In Fig. 2, one can see very small difference between PET/MRI and PET/CT ROIs. However, numerical results shows that liver volume determinate from PET/CT was 858.35 cm3 and from PET/MRI 801.28 cm3. This difference in volume determination and consequently the mass of liver, which is calculated by multiplying volume in cubic centimeter to 0.00103 kg/cm3, has great impact on dosimetry calculations. LDM assumes that all of the energy released by the 90Y beta-particle decay remains within the same voxel. Using the average energy of beta particles, the total energy deposited per unit volume over the entire isotope decay, which is assumed to be infinity due to the permanent implant of microspheres, can be calculated. Calculations give that in each voxel we can assume that the dose in Gy is equal to product of activity in GBq × 49.38/mass (kg) [29]. Here, we used corrected activity for any extra-hepatic distribution such as lung shunting and corrected for residual activity. In this particular case, where tumor was clearly visible in MRI images, we calculated tumor-to-normal tissue (T/N) dose ratio. For this purpose, we used MRI image with tumor ROI to merge with CT images from PET/CT, using deformable transformation provided by MIM software. Although it is beyond the scope of this paper, the T/N ratio in this particular case was 24.90 for PET/CT and 30.00 for PET/MRI study. However, both modalities resulted in a tumor volume about 7.0 cm3 and for such small tumors partial volume effects would greatly affect quantification and dosimetry calculations. The limitation of our approach was that we did not use contrast media in CT nor MRI images. Without contrast media, delineation of lesions and tumors in liver is difficult and not always accurate. Intra hepatic dosimetry, like calculations of T/N ratios, requires using of contrast in anatomical modalities, as well as, PV corrections for lesions smaller than 2.5 cm [19]. Also, for lesions in superior hepatic lobes (Fig. 4), respiratory motion effect can alter 90Y imaging and dosimetry and motion correction should be applied [25].
In clinical settings, in most places around the world, dosimetry related to SIRT with 90Y microspheres is done using simple software provided by vendors. When SIR-Spheres are used, the body surface area (BSA) method is mostly used according which, activity A(GBq) = (BSA − 0.2) × (tumor volume/total liver volume). For TheraSpheres, the LDM is used for total liver or lobe in treatment., i.e., activity A(GBq) is given as a product of dose in Gy multiplied by mass (kg) and divided by 49.38 [29], where a typical dose between 100 and 120 Gy is selected for TheraSphere treatments involving patients with HCC. The target dose for a particular solid tumor is not known, but it is currently believed that this dose range balances the response rate with the risk of hepatic fibrosis.
However, in our study, we have used more sophisticated voxel-based dosimetry calculations, which are providing iso-dose curves and dose-volume histograms (DVH). Such advanced and personalized dosimetry approaches are not reimbursable in many countries, including USA, and these studies are still in research domain only. The optimal software should have good segmentation routine for easy delineation of the liver, other organs, and structures and provide accurate dosimetry calculations for all these volume of interests (VOIs), including iso-dose curves, DVH, minimal, maximal, and average doses. The results also should be easily exported to reports and spreadsheets for further evaluations and comparisons. The same software can also be used in pre-treatment dose estimations, using 99mTc macroaggregated albumin (MAA), mimicking 90Y distribution. However, using MAA to predict 90Y distribution is still an approximation. We believe that we were the first to report that 90Y distribution does not always follow the MAA distribution and that in some situations, there can be large discrepancies between these distributions [30]. Other group went even further and concluded that MAA is not good predictor of 90Y distribution at all [31]. Our opinion is that MAA is useful in predicting 90Y distributions, but the final 90Y distribution can only be confirmed by post-therapy imaging using bSPECT, or even better, using PET/CT or PET/MRI. The main source of MAA and 90Y distribution mismatch, in our experience [32], is attributed to catheter positioning. The role of interventional radiologists is essential in that regard, i.e., in positioning the catheter and avoiding stealing artery branches and critical bifurcations.
Treatment of patients with unresectable primary or metastatic hepatic tumors with 90Y microsphere SIRT continues to develop at a rapid pace. Overcoming technical angiographic challenges, clinical research is expanding indications in many different tumor types. However, fine tuning of 90Y dosimetry and optimizing quantitative imaging in daily practice is still essential. We strongly believe that PET/CT and PET/MRI can fulfill that role of image-based accurate 90Y imaging and dosimetry.