Background: In oncology, lesion characterization is essential for tumor grading, treatment planning, and follow-up of cancer patients. Hybrid imaging systems, such as Single Photon Emission Computed Tomography (SPECT)/CT, Positron Emission Tomography (PET)/CT, or PET/magnetic resonance imaging (MRI), play an essential role for the noninvasive quantification of tumor characteristics. However, most of the existing approaches are challenged by intra-and intertumor heterogeneity. Novel quantitative imaging parameters that can be derived from textural feature analysis (as part of radiomics) are promising complements for improved characterization of tumor heterogeneity, thus, supporting clinically relevant implementations of personalized medicine concepts. Nevertheless, establishing new quantitative parameters for tumor characterization requires the use of standardized imaging objects to test the reliability of results prior to their implementation in patient studies. Methods: In this review, we summarize existing reports on heterogeneous phantoms with a focus on simulating tumor heterogeneity. We discuss the techniques, materials, advantages, and limitations of the existing phantoms for PET, CT, and MR imaging modalities. Conclusions: Finally, we outline the future directions and requirements for the design of cross modality imaging phantoms.
Background PET/MRI phantom studies are challenged by the need of phantom-specific attenuation templates to account for attenuation properties of the phantom material. We present a PET/MRI phantom built from MRI-visible material for which attenuation correction (AC) can be performed using the standard MRI-based AC. Methods A water-fillable phantom was 3D-printed with a commercially available MRI-visible polymer. The phantom had a cylindrical shape and the fillable compartment consisted of a homogeneous region and a region containing solid rods of different diameters. The phantom was filled with a solution of water and [18F]FDG. A 30 min PET/MRI acquisition including the standard Dixon-based MR-AC method was performed. In addition, a CT scan of the phantom was acquired on a PET/CT system. From the Dixon in-phase, opposed-phase and fat images, a phantom-specific AC map (Phantom MR-AC) was produced by separating the phantom material from the water compartment using a thresholding-based method and assigning fixed attenuation coefficients to the individual compartments. The PET data was reconstructed using the Phantom MR-AC, the original Dixon MR-AC, and an MR-AC just containing the water compartment (NoWall-AC) to estimate the error of ignoring the phantom walls. CT-based AC was employed as the reference standard. Average %-differences in measured activity between the CT corrected PET and the PET corrected with the other AC methods were calculated. Results The phantom housing and the liquid compartment were both visible and distinguishable from each other in the Dixon images and allowed the segmentation of a phantom-specific MR-based AC. Compared to the CT-AC PET, average differences in measured activity in the whole water compartment in the phantom of −0.3%, 9.4%, and −24.1% were found for Dixon phantom MR-AC, MR-AC, and NoWall-AC based PET, respectively. Average differences near the phantom wall in the homogeneous region were −0.3%, 6.6%, and −34.3%, respectively. Around the rods, activity differed from the CT-AC PET by 0.7%, 8.9%, and −45.5%, respectively. Conclusion The presented phantom material is visible using standard MR sequences, and thus, supports the use of standard, phantom-independent MR measurements for MR-AC in PET/MRI phantom studies.
Background: Hybrid imaging (e.g., positron emission tomography [PET]/ computed tomography [CT],PET/magnetic resonance imaging [MRI]) helps one to visualize and quantify morphological and physiological tumor characteristics in a single study. The noninvasive characterization of tumor heterogeneity is essential for grading, treatment planning, and following-up oncological patients. However, conventional (CONV) image-based parameters, such as tumor diameter, tumor volume, and radiotracer activity uptake, are insufficient to describe tumor heterogeneities. Here, radiomics shows promise for a better characterization of tumors. Nevertheless, the validation of such methods demands imaging objects capable of reflecting heterogeneities in multi-modality imaging. We propose a phantom to simulate tumor heterogeneity repeatably in PET,CT,and MRI. Methods: The phantom consists of three 50-ml plastic tubes filled partially with acrylic spheres of S1: 1.6 mm, S2: 50%(1.6 mm)/50%(6.3 mm), or S3: 6.3-mm diameter. The spheres were fixed to the bottom of each tube by a plastic grid, yielding one sphere free homogeneous region and one heterogeneous (S1, S2, or S3) region per tube. A 3-tube phantom and its replica were filled with a fluorodeoxyglucose (18F) solution for test-retest measurements in a PET/CT Siemens TPTV and a PET/MR Siemens Biograph mMR system. A number of 42 radiomic features (10 first order and 32 texture features) were calculated for each phantom region and imaging modality. Radiomic features stability was evaluated through coefficients of variation (COV) across phantoms and scans for PET,CT,and MRI.Further,the Wilcoxon test was used to assess the capability of stable features to discriminate the simulated phantom regions. Results: The different patterns (S1-S3) did present visible heterogeneity in all imaging modalities. However, only for CT and MRI, a clear visual difference was present between the different patterns. Across all phantom regions in PET, CT, and MR images, 10, 16, and 21 features out of 42 evaluated features in total had a COV of 10% or less. In particular, CONV, histogram, and gray-level run length matrix features showed high repeatability for all the phantom regions and imaging modalities. Several of repeatable texture features allowed the image-based discrimination of the different phantom regions (p < 0.05). However, depending
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