Development of a Patient-specific Tumor Mold Using Magnetic Resonance Imaging and 3-Dimensional Printing Technology for Targeted Tissue Procurement and Radiomics Analysis of Renal Masses

Abstract

Objective: To implement a platform for colocalization of in vivo quantitative multiparametric magnetic resonance imaging features with ex vivo surgical specimens of patients with renal masses using patient-specific 3-dimensional (3D)-printed tumor molds, which may aid in targeted tissue procurement and radiomics and radiogenomic analyses.

Materials and methods: Volumetric segmentation of 6 renal masses was performed with 3D Slicer (http://www.slicer.org) to create a 3D tumor model. A slicing guide template was created with specialized software, which included notches corresponding to the anatomic locations of the magnetic resonance images. The tumor model was subtracted from the slicing guide to create a depression in the slicing guide corresponding to the exact size and shape of the tumor. A customized, tumor-specific, slicing guide was then printed using a 3D printer. After partial nephrectomy, the surgical specimen was bivalved through the preselected magnetic resonance imaging (MRI) plane. A thick slab of the tumor was obtained, fixed, and processed as a whole-mount slide and was correlated to multiparametric MRI findings.

Results: All patients successfully underwent partial nephrectomy and adequate fitting of the tumor specimens within the 3D mold was achieved in all tumors. Distinct in vivo MRI features corresponded to unique pathologic characteristics in the same tumor. The average cost of printing each mold was US$160.7 ± 111.1 (range: US$20.9-$350.7).

Conclusion: MRI-based preoperative 3D printing of tumor-specific molds allow for accurate sectioning of the tumor after surgical resection and colocalization of in vivo imaging features with tissue-based analysis in radiomics and radiogenomic studies.

Figure 1

A 3D object was generated by the model maker module in 3D Slicer and saved in the standard tessellation language (STL) file format. (A) The green-colored and brown-colored objects represent the STLs for the mold and tumor, respectively. (B) Zoomed-in image illustrating the notch in the mold (arrow) corresponding to the location of the preselected MRI image plane for radiomic analysis. (C) Printed mold using 3D printer with labeling on the anterior side (arrow). (D) Slicing of tumor positioned within the 3D mold at the level of the notch (arrow). (E) Tumor specimen after sectioning is positioned anatomically. Tissue samples can then be obtained from specific co-localized areas to the MRI findings.

Figure 2

Building model for 3D printing. Representative images using a positive mold (red, top) versus a negative mold (green, bottom) of the tumor. The anterior side of the 3D mold is indicated by the green and orange circles, respectively. Fitting of the tumor on a positive mold may be challenged by various amounts of perirenal fat around the tumor specimen. In contrast, the inner aspect of the tumor (i.e. interface with the renal parenchyma) tends to be more predictable.

Figure 3

Clear cell RCC (ISUP grade 3) in a 49-years-old male patient. Coronal T2-weighted single-shot turbo spin echo image (A), arterial spin labelled (ASL) perfusion map (B), and T1-weighted spoiled gradient echo image acquired during the corticomedulary phase (C) of a dynamic contrast enhanced examination show a heterogeneous mass in the upper pole of right kidney. Note the different morphologic features in the tumor with a solid hypervascular component superiorly (arrows) and a non-vascularized area inferiorly (*). (D) Tumor specimen positioned within the 3D mold indentation after resection and spatial orientation using fiducials (i.e. staples) placed during surgery. The desired location for cutting the specimen corresponding to the location of MRI images (A–C) is indicated by the notch (arrow) and the anterior aspect of the mass is also noted in the mold (arrowhead). (E) Section of gross specimen demonstrating golden yellow solid (arrows) and gelatinous friable (*) components in the mass corresponding to the MRI features in vivo. (F) Whole-mount histopathologic H&E slide confirms the presence of a large solid component superiorly (arrows) and necrosis inferiorly (*). Note that the necrotic space is partially collapsed after sectioning. (G) Histopathology of solid area of the tumor shows morphologic features characteristic of clear cell RCC. The tumor cells are arranged in nested architecture with vascular septae. The cells have eosinophilic to clear cytoplasm, round nucleus and prominent grade 3 nucleoli. (H) The gelatinous areas consist of eosinophilic amorphous cellular debris with cystic degeneration. No viable tumor cells or fibrosis is identified.

Fig. 4

Clear cell RCC (ISUP grade 2) in a 50-year-old female patient. Coronal T1-weighted spoiled gradient echo images acquired during the corticomedulary (A) and delayed nephrographic (B) phases of a dynamic contrast enhanced examination show a heterogeneous mass at the upper pole of right kidney exhibiting a hypervascular component peripherally (arrowheads). A central stellate area with intense delayed enhancement (*) is present. Coronal perfusion map (C) generated with a 2D ASL acquisition shows high perfusion in the periphery of the mass inferiorly (arrowheads) with areas of decreased tumor perfusion centrally (*). Bivalved gross specimen confirms the presence of a rim of viable tumor tissue (arrowhead) around a central scar (*) (D). E) Histopathology in viable tumor showed prototypic clear cell renal cell carcinoma, ISUP nucleolar grade 2, with nests of clear cells surrounded by intricate branching vascular network (F). Sections from the central scar show hyalinization and fibrosis with branching capillary network. No viable tumor cells or necrosis is identified. (G).