Development of scalable lymphatic system in the 4D XCAT phantom: Application to quantitative evaluation of lymphoma PET segmentations.

Background: Digital anthropomorphic phantoms, such as the 4D extended cardiac-torso (XCAT) phantom, are actively used to develop, optimize, and evaluate a variety of imaging applications, allowing for realistic patient modeling and knowledge of ground truth. The XCAT phantom defines the activity and attenuation for a simulated patient, which includes a complete set of organs, muscle, bone, and soft tissue, while also accounting for cardiac and respiratory motion. However, the XCAT phantom does not currently include the lymphatic system, critical for evaluating medical imaging tasks such as sentinel node detection, node density measurement, and radiation dosimetry.

Purpose: In this study, we aimed to develop a scalable lymphatic system in the XCAT phantom, to facilitate improved research of the lymphatic system in medical imaging. Using this scalable lymphatic system, we modeled the lymph node conglomerate pathology that is characteristically observed in primary mediastinal B-cell lymphoma (PMBCL). As an extended application, we evaluated positron emission tomography (PET) image quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of these simulated lymphomas, though the phantoms may be applied to other imaging modalities and study design paradigms (e.g., image quality, detection).

Methods: A template model for the lymphatic system was developed based on anatomical data from the Visible Human Project of the National Library of Medicine. The segmented nodes and vessels were fit with non-uniform rational basis spline surfaces, and multichannel large deformation diffeomorphic metric mapping was used to propagate the template to different XCAT anatomies. To model conglomerates observed in PMBCL, lymph nodes were enlarged, converged within the mediastinum, and tracer concentration was increased. We used the phantoms as inputs to a PET simulation tool, which generated images using ordered subsets expectation maximization reconstruction with 2-8 mm Gaussian filters. Fixed thresholding (FT) and gradient segmentation were used to determine MTV and TLG. Percent bias (%Bias) and coefficient of variation (COV) were computed as measures of accuracy and precision, respectively, for each MTV and TLG measurement.

Results: Using the methodology described above, we introduced a scalable lymphatic system in the XCAT phantom, which allows for the radioactivity and attenuation ground truth to be generated in 116 ± 2.5 s using a 2.3 GHz processor. Within the Rhinoceros interface, lymph node anatomy and function were modified to create a cohort of 10 phantoms with lymph node conglomerates. Using the lymphoma phantoms to evaluate PET quantification of MTV, mean %Bias values were -9.3%, -41.3%, and 20.9%, while COV values were 4.08%, 7.6%, and 3.4% using 25% FT, 40% FT, and gradient segmentations, respectively. Comparatively for TLG, mean %Bias values were -27.4%, -45.8%, and -16.0%, while COV values were 1.9%, 5.7%, and 1.4%, for the 25% FT, 40% FT, and gradient segmentations, respectively.

Conclusions: In this work, we upgraded the XCAT phantom to include a lymphatic system, comprised of a network of 276 scalable lymph nodes and corresponding vessels. As an application, we created a cohort of phantoms with lymph node conglomerates to evaluate lymphoma quantification in PET imaging, which highlights an important application of this work.