PixelPrint: Three-dimensional printing of realistic patient-specific lung phantoms for validation of computed tomography post-processing and inference algorithms

Background Radiomics and other modern clinical decision-support algorithms are emerging as the next frontier for diagnostic and prognostic medical imaging. However, heterogeneities in image characteristics due to variations in imaging systems and protocols hamper the advancement of reproducible feature extraction pipelines. There is a growing need for realistic patient-based phantoms that accurately mimic human anatomy and disease manifestations to provide consistent ground-truth targets when comparing different feature extraction or image cohort normalization techniques. Materials and Methods PixelPrint was developed for 3D-printing lifelike lung phantoms for computed tomography (CT) by directly translating clinical images into printer instructions that control the density on a voxel-by-voxel basis. CT datasets of three COVID-19 pneumonia patients served as input for 3D-printing lung phantoms. Five radiologists rated patient and phantom images for imaging characteristics and diagnostic confidence in a blinded reader study. Linear mixed models were utilized to evaluate effect sizes of evaluating phantom as opposed to patient images. Finally, PixelPrint’s reproducibility was evaluated by producing four phantoms from the same clinical images. Results Estimated mean differences between patient and phantom images were small (0.03-0.29, using a 1-5 scale). Effect size assessment with respect to rating variabilities revealed that the effect of having a phantom in the image is within one-third of the inter- and intra-reader variabilities. PixelPrint’s production reproducibility tests showed high correspondence among four phantoms produced using the same patient images, with higher similarity scores between high-dose scans of the different phantoms than those measured between clinical-dose scans of a single phantom. Conclusions We demonstrated PixelPrint’s ability to produce lifelike 3D-printed CT lung phantoms reliably. These can provide ground-truth targets for validating the generalizability of inference-based decision-support algorithms between different health centers and imaging protocols, as well as for optimizing scan protocols with realistic patient-based phantoms. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement ACKNOWLEDGEMENT We acknowledge support through the National Institutes of Health (R01-CA-249538, R01-CA-264835-01, and R01-EB-030494). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: University of Pennsylvania Institutional Review Board 3600 Civic Center Blvd., 9th Floor Philadelphia, PA 19104 Phone: 215-573-2540 (Federalwide Assurance # 00004028) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors