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Method Article

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

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DOI:

10.3791/50403

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July 29th, 2013

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In This Article

Summary

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).

Abstract

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.

Introduction

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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Protocol

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 prepared to cast the tumor-simulating test objects as described in this section 7. All acrylic plates and rods required for preparation of the sil....

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Results

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 initial mass was 101.02 g. The size of the phantom .......

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Discussion

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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Disclosures

No conflicts of interest declared.

Acknowledgements

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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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Reagent/Material 
PVC pipeN/AN/AHome Depot
Bolt, nut, washer and metal platesN/AN/AHome Depot
Acrylic plates and rodsN/AN/APlastic supply in San Antonio, TX
Steel ballsNordex, Inc.AEC-M2-2, -4, -7, -10 and -142, 4, 7, 10 and 14 mm diameter
C-clampsAdjustable Clamp1420-C2 inch length
Masking tape3M Industrial Adhesives and Tapes2600 
Duct tape3M Industrial Adhesives and TapesS-3763SIL 
J-B KWIKJ-B WELD Co.380238 
3M Scotch-Weld Epoxy Adhesive3M Industrial Adhesives and TapesDP-100 
Silicone greasePermatex, Inc.22058 
Silicone glueDAP, Inc.688 
Silicone rubber compoundSmooth-ON, Inc.Smooth-SilTM950 Part A and BA:B mix ratio = 10:1 by weight
BrushN/AN/AHobby Lobby
SyringeBecton Dickinson30960410 ml
NeedleBecton Dickinson30515622-gauge 1.5 inch length
FunnelN/AN/A 
Mesh filtersSmall parts, Inc.CMN-0010-C and CMN-0020-C10 and 20 μm
Whole milkN/AN/AHEB in San Antonio, TX
ThimerosalSigma-Aldrich Co.T5125 
PropanolSigma-Aldrich Co.33538 
EDTASigma-Aldrich Co.431788 
CuCl2Sigma-Aldrich Co.459097 
AgaroseSigma-Aldrich Co.A0169 
BaSO4Sigma-Aldrich Co.B8675 
Glass beadsPotters Industries, Inc.3000E 
PET/AL/LLDPE*Pechiney Plastic Packaging, Inc.Pechiney Spec 151Phantom cover material
 *Polyethylene terephthalate/aluminum/linear low density polyethylene
Equipment 
Rotisserie motorBrinkmann812-7103-SHome Depot
Water bath 1Precision, Inc.Model: 282, Serial #: 601091552 
Water bath 2VWR, Inc.Model: 1212, Serial #: 08119606 
UltrasoundVisualsonicsSerial #: 770/120-259 
CTGamma Medica-IdeasSerial #: GR 0050 
MRIBrukerPart #: W3301390, Serial #: 0030 

References

  1. Prasad, S. R., et al. CT tumor measurement for therapeutic response assessment: Comparison of unidimensional, bidimensional, and volumetric techniques-Initial observations. Radiology. 225 (2), 416-419 (2002).
  2. Cortes, J., et al.

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