A calibration CT mini‐lung‐phantom created by 3‐D printing and subtractive manufacturing

Abstract We describe the creation and characterization of a calibration CT mini‐lung‐phantom incorporating simulated airways and ground‐glass densities. Ten duplicate mini‐lung‐phantoms with Three‐Dimensional (3‐D) printed tubes simulating airways and gradated density polyurethane foam blocks were designed and built. Dimensional accuracy and CT numbers were measured using micro‐CT and clinical CT scanners. Micro‐CT images of airway tubes demonstrated an average dimensional variation of 0.038 mm from nominal values. The five different densities of incorporated foam blocks, simulating ground‐glass, showed mean CT numbers (±standard deviation) of −897.0 ± 1.5, −844.1 ± 1.5, −774.1 ± 2.6, −695.3 ± 1.6, and −351.0 ± 3.7 HU, respectively. Three‐Dimensional printing and subtractive manufacturing enabled rapid, cost‐effective production of ground‐truth calibration mini‐lung‐phantoms with low inter‐sample variation that can be scanned simultaneously with the patient undergoing lung quantitative CT.


| INTRODUCTION
The use of quantitative CT continues to expand in lung disease, being increasingly applied to interstitial and alveolar processes such as obstruction, emphysema, fibrosis, and opacification. [1][2][3][4][5] Measurements of airways thicknesses and parenchymal densities are vital in diffuse lung disease 6 and recently the quantification of parenchymal opacification has been shown to predict adverse outcome in COVID-19 pneumonia. 7 However, uncertainty is an inherent aspect of quantification with CT imaging, being introduced by such variations as from scanner hardware, scanning protocols, reconstruction algorithms, patient body habitus, and potentially further compounded by justifiable efforts to reduce CT doses to as low as reasonably achievable (ALARA). [8][9][10] Accuracy in lung density and airways measurements have been shown to be influenced by a variety of technical factors in CT acquisitions. 11,12 One strategy to reduce the aforementioned uncertainties is to scan a calibration phantom simultaneously with patients. Nelson et al. used a phantom with calcium inserts to adjust for CT number differences in coronary artery calcium CT. 13 Henschke et al. scanned a pocket phantom embedded with Teflon sphere with patients who underwent lung cancer CT to investigate the variations in tumor volume measurement. 14 To achieve a desired improvement in either CT attenuation quantification or geometrical assessment of pathologies, the characteristics of the calibration phantom must be tailored to the specific clinical tasks. Three-Dimensional (3-D) printing (also known as additive manufacturing) offers unique advantages over traditional machining techniques (also known as subtractive manufacturing). Three-Dimensional printing facilitates rapid prototyping of complex designs, with dimensional accuracy possible to the tens of micrometers. 15 printing has enabled the creation of numerous models used for education and pre-surgical planning, and is beginning to enable CT phantom creation. [17][18][19] In this work, we apply the advantages of both 3-D printing and traditional machining to create a set of 10 duplicate calibration minilung-phantoms incorporating tubes that simulate distal airways and gradated density polyurethane foam blocks that simulate a range of parenchymal ground-glass densities encountered in healthy and diseased lungs. The geometrical accuracy of 3-D printed simulated airway tubes in mini-lung-phantoms was quantified with high-resolution micro-CT, and the CT number of machined ground-glass density blocks and geometrical accuracy of airway tubes were evaluated on clinical CT scanners from two CT manufacturers.

2.A | Mini-lung-phantom creation
No IRB review was required for this phantom study. The dimensions of the tubes simulating large to small airways (nominal inner diameters of 5, 4, 3, 2, 1 mm; with corresponding nominal outer diameters of 9.6, 7.6, 5.6, 3.6, 1.8 mm, respectively) were based on previous airways phantoms designed for dimensional measurement accuracy quality control in chest CT, with tube dimensions approximating distal bronchi and bronchioles. [20][21][22] Aside from tube dimensions, the minilung-phantom is designed to be much smaller (1.75 × 1.75 × 12 cm) than conventional airways phantoms given the current intent of the mini-lung-phantom being placed on patients and scanned simultaneously. The mini-lung-phantom design was drafted by computer-aided design (SolidWorks, Dassault Systèmes, Vélizy-Villacoublay Cedex, France) [ Fig. 1(a)]. The engineering file was translated to standard tessellation language (STL) for 3-D printing using a Viper stereolithography machine (3D Systems, Rock Hill, SC, USA) on high-resolution mode using Accura ClearVue resin (Autotiv Manufacturing, Salem, NH). Three-Dimensional printing produced the shell, simulated airways tubes, and lid assembly of the mini-lung-phantom. As the current limitations of 3-D printing technology prevent consistent and accurate reproduction of clinically relevant ground-glass densities, polyurethane foam was used; and five different rigid polyurethane foam blocks from the same respective manufacturing batches with nominal densities of 0.096, 0.160, 0.240, 0.320, and 0.641 g/cm 3 (General Plastics, Tacoma, WA, USA) were machined into 1.5 cm cubes (WeCutFoam, Sunnyvale, CA) and inserted in the described order within the shell of the 3-D printed mini-lung-phantoms (numbered as foam blocks 1, 2, 3, 4, 5), respectively [ Fig. 1(a)]. Polyurethane foams from the same manufacturer have been validated for use in CT scanning previously. 23,24 Phenolic micro-balloons (MAS Epoxies, South St. Paul, MN, USA) at −905 HU density was poured into the 3-D printed cavity adjacent to the tube containing compartment of the mini-lung-phantom to simulate surrounding lung density. Finally, the lid was sealed to the body of the assembly using ethyl-2-cyanoacrylate adhesive [ Fig. 1(b)]. Ten duplicate calibration mini-lung-phantoms were created.

2.B | Micro-CT imaging protocol
Micro-CT scanning of all 10 mini-lung-phantoms was performed using an eXplore CT120 scanner (TriFoil Imaging, Chatsworth, CA, USA). Cone-beam CT scans were performed at 2 × 2 binning, 70 kV, 40 mA, with 720 views acquired in a 360-degree scan. Axial images were reconstructed with an isotopic 50 µm voxel size.

2.E | Ground-glass foam blocks density analyses
Average CT numbers were measured in a square region of interest

| RESULTS
3D-printed and machined components were assembled to produce 10 identical mini-lung-phantoms. Figure 1 shows the design schematic, photograph, clinical CT appearance, and unit dimensional and density specifications of the calibration mini-lung-phantom. The close-up photo, micro-CT, and clinical CT images of the airways mimicking tubes are shown in Fig. 2. Table 1  For comparable dose levels, the average CT numbers differed by at most 3.0 HU between the two scanners (  Three-dimensional printing of imaging phantoms is being increasingly reported, ranging from simulated low-contrast soft tissue lesions 32 to whole thoracic phantoms for radiation treatment planning. 18 The average dimensional error of the 3-D printed tubes in this work at 0.038 mm is superior to the average error of comparable tubes made from traditional machining with an average absolute error of 0.11 mm. 22 As that 3-D printing in this work was carried

| CONCLUSION
In summary, calibration CT mini-lung-phantoms incorporating simulated airways and ground-glass lung densities were created using 3-D printing and conventional machining. This phantom has the potential to facilitate monitoring and help decrease uncertainty in quantitative lung CT.

ACKNOWLEDGMENTS
The authors thank Heidi Chang, Kyle Gifford, and Tim Doyle for assistance with conception/design, 3-D printing, and micro-CT acquisition, respectively.
Data sharing is not applicable to this article as no new data were created or analyzed in this study.

CONF LICT OF I NTEREST
No conflicts of interest.

A U T H O R C O N T R I B U T I O N
H. Henry Guo.
• Substantial contributions to the conception or design of the work; and the acquisition, analysis, and interpretation of data for the work; • Drafting the work or revising it critically for important intellectual content; • Final approval of the version to be published; • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
• Analysis and interpretation of data for the work; • Drafting the work or revising it critically for important intellectual content; • Final approval of the version to be published; • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
• Analysis and interpretation of data for the work; • Drafting the work or revising it critically for important intellectual content; • Final approval of the version to be published; • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
• Analysis and interpretation of data for the work; • Drafting the work or revising it critically for important intellectual content; • Final approval of the version to be published; • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
• Substantial contributions to the conception or design of the work; • Drafting the work or revising it critically for important intellectual content; • Final approval of the version to be published; • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
• Substantial contributions to the conception or design of the work; and the acquisition, analysis, and interpretation of data for the work; • Drafting the work or revising it critically for important intellectual content; • Final approval of the version to be published; • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

| DISCLOSURE STATEMENT
"MP is former shareholder in Prismatic Sensors AB and was visiting researcher with General Electric Company in 2019-2020, funded by the EU Research Executive Agency." None of these activities are related to the present article.