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Summary

Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Bioengineering

Construction of a Preclinical Multimodality Phantom Using Tissue-mimicking Materials for Quality Assurance in Tumor Size Measurement

Published: July 29th, 2013

DOI:

10.3791/50403

1Department of Radiation Oncology, University of Kansas School of Medicine, 2Department of Radiology, University of Texas Health Science Center at San Antonio

This paper describes in-house procedures of constructing a preclinical multimodality phantom made of tissue-mimicking (TM) materials for quality assurance (QA) of tumor size measurement in animal imaging modalities such as ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI).

World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for radiologic assessment of solid tumors in response to anti-tumor drug therapy in the 1980s and 1990s, respectively. WHO criteria measure solid tumors in two-dimensions, whereas RECIST measurements use only one-dimension which is considered to be more reproducible 1, 2, 3,4,5. These criteria have been widely used as the only imaging biomarker approved by the United States Food and Drug Administration (FDA) 6. In order to measure tumor response to anti-tumor drugs on images with accuracy, therefore, a robust quality assurance (QA) procedures and corresponding QA phantom are needed.

To address this need, the authors constructed a preclinical multimodality (for ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) phantom using tissue-mimicking (TM) materials based on the limited number of target lesions required by RECIST by revising a Gammex US commercial phantom 7. The Appendix in Lee et al. demonstrates the procedures of phantom fabrication 7. In this article, all protocols are introduced in a step-by-step fashion beginning with procedures for preparing the silicone molds for casting tumor-simulating test objects in the phantom, followed by preparation of TM materials for multimodality imaging, and finally construction of the preclinical multimodality QA phantom. The primary purpose of this paper is to provide the protocols to allow anyone interested in independently constructing a phantom for their own projects. QA procedures for tumor size measurement, and RECIST, WHO and volume measurement results of test objects made at multiple institutions using this QA phantom are shown in detail in Lee et al. 8.

Assessment of the change in tumor size is an important endpoint for evaluating the activity of anti-tumor drugs in both tumor shrinkage and disease progression 9, 10. World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) are the codified methods for the anatomic assessment of tumor lesions in imaging modalities such as ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI). For WHO criteria, the product of tumor maximum diameter and its largest perpendicular diameter in the transverse plane for target regions is calculated 4. In contrast, for RECIST, the sum of longest diameters ....

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1. Phantom Design

A drawing of the preclinical multimodality phantom is shown in Figure 1 7, 8. The size of the phantom is 38 mm in diameter and 115 mm in length to allow the phantom to be scanned in various animal scanners. The phantom contains five tumor-simulating test objects (diameter: 14, 10, 7, 4 and 2 mm) placed at a depth of 10 mm within the phantom.

2. Silicone Mold Construction

Silicone molds are prepare.......

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Figure 3B and Figure 5 show two silicone molds for casting test objects, and the multimodality phantom, respectively. The length × width × depth of each mold is 109 mm × 37 mm × 21 mm and two molds are identical mirror-images. One mold has 1 mm holes where TM material can be inserted using a thin needle. Each mold has an additional five holes for alignment rods. The length × width × depth of the phantom is 115 mm × 38 mm × 24 mm and its ini.......

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The goal of this article was to provide the methods for making TM materials for multimodality imaging and constructing a preclinical multimodality phantom as a QA tool for accurate tumor size measurement using different modalities in multiple institutions. As previously mentioned, TM materials were originally developed by Dr. Ernest L. Madsen's laboratory at the University of Wisconsin Madison for a multi-imaging modality prostate phantom. We modified Dr. Madsen's TM material protocols for our own purpose in order to hav.......

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The authors are thankful to Dr. Madsen at the University of Wisconsin-Madison and Cristel Baiu at Gammex Inc. for providing advice on TM materials. The authors are also grateful to Dr. Malcolm David Murray for providing the methods to construct the phantom.

....

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Name Company Catalog Number Comments
Reagent/Material      
PVC pipe N/A N/A Home Depot
Bolt, nut, washer and metal plates N/A N/A Home Depot
Acrylic plates and rods N/A N/A Plastic supply in San Antonio, TX
Steel balls Nordex, Inc. AEC-M2-2, -4, -7, -10 and -14 2, 4, 7, 10 and 14 mm diameter
C-clamps Adjustable Clamp 1420-C 2 inch length
Masking tape 3M Industrial Adhesives and Tapes 2600  
Duct tape 3M Industrial Adhesives and Tapes S-3763SIL  
J-B KWIK J-B WELD Co. 380238  
3M Scotch-Weld Epoxy Adhesive 3M Industrial Adhesives and Tapes DP-100  
Silicone grease Permatex, Inc. 22058  
Silicone glue DAP, Inc. 688  
Silicone rubber compound Smooth-ON, Inc. Smooth-SilTM950 Part A and B A:B mix ratio = 10:1 by weight
Brush N/A N/A Hobby Lobby
Syringe Becton Dickinson 309604 10 ml
Needle Becton Dickinson 305156 22-gauge 1.5 inch length
Funnel N/A N/A  
Mesh filters Small parts, Inc. CMN-0010-C and CMN-0020-C 10 and 20 μm
Whole milk N/A N/A HEB in San Antonio, TX
Thimerosal Sigma-Aldrich Co. T5125  
Propanol Sigma-Aldrich Co. 33538  
EDTA Sigma-Aldrich Co. 431788  
CuCl2 Sigma-Aldrich Co. 459097  
Agarose Sigma-Aldrich Co. A0169  
BaSO4 Sigma-Aldrich Co. B8675  
Glass beads Potters Industries, Inc. 3000E  
PET/AL/LLDPE* Pechiney Plastic Packaging, Inc. Pechiney Spec 151 Phantom cover material
      *Polyethylene terephthalate/aluminum/linear low density polyethylene
Equipment      
Rotisserie motor Brinkmann 812-7103-S Home Depot
Water bath 1 Precision, Inc. Model: 282, Serial #: 601091552  
Water bath 2 VWR, Inc. Model: 1212, Serial #: 08119606  
Ultrasound Visualsonics Serial #: 770/120-259  
CT Gamma Medica-Ideas Serial #: GR 0050  
MRI Bruker Part #: W3301390, Serial #: 0030  

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