Phantom design
Key criteria in the design of the imaging phantom were considered. The phantom should be anatomically realistic and simulate a patient abdomen, both visually and when imaged with scintigraphy and x-ray computed tomography. A fillable section within the structure was required to represent activity distributions within a liver. The liver section needed to accommodate multiple inserts for lesion representation and allow flexibility in insert arrangement while allowing reproducible assembly for repeated studies. All materials used in the phantom must have similar densities and attenuation coefficients to tissue. The material for the lesions should also be transparent for visualisation and ease of filling. Filling and assembly should be uncomplicated to reduce radiation exposure when preparing the phantom. When filled, the material should have low water absorption, be water tight at all seals and be sufficiently strong to maintain structural integrity when filled and transported. Finally, a total weight limit to the phantom was specified as 20 kg to ensure transportation and manual handing constraints were met.
Mean liver volume of patients undergoing SIRT were taken from that measured by Theysohn et al. [11]. The abdomen of a 32-year-old male volunteer with an appropriate liver volume and anatomy for representation of the patient cohort was then selected. Anatomical data were obtained from a 24-s T1-weighted volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.5 T MRI scanner, giving an in-plane pixel size of 0.7- and 2.8-mm contiguous slices. The required organ volumes were generated from the anatomical dataset and converted to the appropriate file format using a methodology similar to that previously described [10]. Organs were delineated and segmented on the Hermes Hybrid Viewer 2.2c image processing software (Stockholm, Sweden) to create a new dataset containing only the required outlined volumes (liver, lungs and abdominal trunk). Figure 1a, b shows the original MR slice and segmented organ outlines. Organ volumes were exported to the Delft Visualization and Image processing Development Environment (DeVide) [12] for smoothing and surface rendering (Fig. 1c). To remove the MR pixelation, the 3D surface mesh was smoothed (Fig. 1d) and saved as a binary stereo lithography (STL) file. The STL files were imported into the Autodesk Meshmixer software (Autodesk Inc.) and the organ volumes subtracted from the abdominal trunk, to create a fillable liver cavity. To ensure sufficient wall thickness in the phantom between the liver and the lungs, the liver volume was relocated 5 mm in an inferior direction prior to subtraction from the main body. A removable base was designed to allow access into the liver cavity and connection points positioned for placing lesion inserts. A flow diagram illustrating the image processing procedure is given in Fig. 2, indicating the software tools used and data file type at each processing step. Unlike previous designs [10], which use a modular assembly of fillable organ shells, the solid abdominal trunk with liver void of the Abdo-Man phantom means the phantom is more robust and should be less prone to damage during transport and filling.
Spherical lesion inserts were designed for insertion into the finished phantom using the Meshmixer software. Spheres with diameters of 10, 20, 30, 40 and 50 mm were designed with 1-mm wall thicknesses. Spheres were designed to be connected to the base with detachable support rods which attach to the spheres via connection ports with M6 screw fittings. One-millimetre holes at the connection points on the spheres allow the inserts to be emptied or filled with a 4-in. (102 mm) 19-gauge needle, and the hole is then sealed when the support rod is connected. Figures 3 and 4 illustrate the sphere designs and how they are assembled within the phantom. Once assembled, the liver void can be filled via an access port in the base of the phantom. For consecutive acquisitions with varying concentrations in the liver, addition activity can be added as necessary. This procedure is quicker and simpler than required by alternative designs whereby the phantom may need to be dismantled to access the liver section.
In addition to simple spheres, more complex inserts were also designed, including:
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a)
Forty-millimetre hollow sphere with 25-mm solid inner sphere to represent the deposition of microspheres in the neovascular rim of the tumour around a necrotic core.
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b)
Forty-millimetre hollow sphere with the outer rim being divided into two compartments. This represents lesions where arterial feeding happens through different arterial networks—such as the left hepatic and right hepatic arteries.
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c)
Forty-millimetre internal sphere where the external shell has a 1-cm circular area which is entirely blocked off. This simulates small regions of a lesion where microspheres are not deposited.
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d)
Forty-millimetre-diameter hollow sphere, 1-mm wall thickness, with internal hollow sphere also with 1-mm wall thickness and internal diameter of 25 mm. Each sphere can be filled independently.
Schematic images of these inserts are shown in Fig. 5.
Phantom production
The phantom was printed using a Connex3 PolyJet printer (Stratasys Ltd., Eden Prairie, MN, USA). A 16-μm layer of liquid ultraviolet-curable photopolymer is printed onto the build tray. An ultraviolet laser then cures the resin solidifying the pattern traced on the tray. This process is then repeated for each layer. Where overhangs or domed shapes are required, a removable support material is printed on the under layers to prevent the structure collapsing before curing. Various photopolymer resins are available for printing; in this case, a white opaque resin was chosen for the main phantom body (VeroWhite Plus FullCure 835). A black rubber-like material (TangoBlack Plus FullCure 980 Shore 27a) was printed alongside the main phantom material to create gaskets to seal the phantom around the base and screw fittings. Lesion inserts were printed using a transparent polymer, (VeroClear FullCure 810) to enable liquid level to be observed during filling.
Material properties
To test the suitability of the photopolymers prior to printing, material properties reported by the manufacturer were compared to those more commonly used in phantom production. In addition, cubic test objects were printed and the density and CT Hounsfield units measured. Composition of the print material has previously been reported as a mixture of acrylic monomers and oligomers, with a small proportion (<2.5 %) of a photo-initiator [10]. As the photo-initiator is subject to intellectual property, no information regarding elemental composition is available. An estimate of material attenuation at isotope energies was estimated assuming that the monomer/oligomer mixture has a similar effective atomic number to polymethylmethacrylate (PMMA) and substituting the unknown initiator for materials with different effective atomic numbers as an input into the NIST X-COM program [13]. The effective atomic number of the unknown initiator was increased until the outputted material attenuation corresponded to that measured on CT.
Phantom geometry
To verify that the phantom was a true representation of the original anatomy, comparisons were made against the original MR dataset. Post production, the volume of water required to fill the phantom was compared to the outlined volume measured on MR. X-ray CT images of the phantom were also acquired and a visual inspection of the CT and MR datasets performed. Transaxial slices through the liver section were compared and diametrical measurements of the liver and abdominal trunk made using the Hermes Hybrid Viewer 2.2c image processing software (Stockholm, Sweden).
Phantom imaging and dosimetry
To demonstrate the application of the phantom, multimodality imaging was performed with Y-90 SPECT/CT bremsstrahlung, Y-90 PET/CT and Tc-99m SPECT/CT. Three different lesion designs were used within the phantom: a 20-mm sphere, a 40-mm sphere and a 40-mm hollow sphere with 25-mm solid inner sphere. For the Y-90 imaging, the liver section of the phantom was filled with 500 MBq of Y-90 chloride, mixed with 0.2 g of disodium ethylenediaminetetraacetic acid (EDTA) injection to ensure a uniform mixture at 0.29 MBq/ml. Lesion inserts were filled with the appropriate concentration of Y-90 solution (1.72 MBq/ml) to give a final liver-to-lesion concentration ratio of 1:6. Y-90 activities were determined from a stock solution measured under calibration conditions with a Fidelis secondary standard dose calibrator. Dilution activities and subsequent concentrations were determined using accurate mass measurements made during dispensing. A similar procedure was carried out to prepare the phantom for Tc-99m imaging using a total activity of 200-MBq Tc-99m pertechnetate.
Y-90 PET/CT imaging of the phantom was performed as described by Willowson et al. [14] on a Siemens Biograph mCT scanner using a Na-22 isotope selection (as Y-90 was not an available option). Two bed positions acquired at 15 min were sufficient to cover the phantom length. Images were reconstructed using an ordered subset expectation maximization (OSEM) iterative reconstruction algorithm, 2 iterations and 16 subsets, with TOF and PSF correction. The final image size was a 200 × 200 matrix with 4-mm voxels smoothed with a 4-mm Gaussian kernel.
Y-90 bremsstrahlung imaging was performed on a Siemens Symbia Intevo SPECT/CT scanner fitted with medium-energy general purpose collimators. Acquisitions were acquired with 72 projections at 20 s each. Energy window settings were chosen based on the work by Heard et al. [15] and covered an energy range of 56–268 keV. Images were reconstructed with an OSEM iterative reconstruction algorithm, 4 iterations and 8 subsets, with a PSF correction and CT attenuation correction. Ideally, PSF correction would be based on a measured bremsstrahlung PSF; however, this was not available in this version of reconstruction software. Instead, a theoretical 2D Gaussian kernel, adjusted for septal penetration, is applied based on the centroid energy of the window and the medium-energy collimator.
Tc-99m SPECT/CT of the phantom was carried out to demonstrate the comparative image quality of MAA over therapy imaging. SPECT/CT was performed using a similar protocol to the bremsstrahlung imaging using LEHR collimators and a 15 % energy window centred at 140 keV.
Image analysis and absorbed dose calculations for all three lesions and imaging methodologies were performed using the partition model [16] and in three dimensions using the local deposition method [17]. For the bremsstrahlung and Tc-99m imaging, quantification was achieved using the total counts within the liver and the known phantom activity. Quantification of the PET imaging was performed using the inbuilt calibration factors and scaling the reconstructed image according to the known branching ratio of Y-90 and Na-22. Measured absorbed dose distributions were compared to a “reference dose distribution” derived from the known activity in each phantom compartment and the OEDIPE [18] dosimetry interface tool for MCNPX2.5 Monte Carlo (MC) simulations. Throughout all filling and scanning protocols, finger and body TLDs were worn as standard practice. No excess doses to the operators were reported by the radiation dosimetry service.