Breast phantom design for X-ray phase-contrast imaging
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Breast cancer is one of the most diffuse diseases and its incidence rate is increasing. Mammography is the gold standard exam for screening breast cancer. Nevertheless, to provide better conditions for visualization and detection of tumors, in particular to young women, techniques exploiting the X-ray phase contrast to generate images have been studied and proposed for clinical use. As every imaging modality clinically implemented, the capabilities and limitations of an X-ray phase-contrast system dedicated to breast imaging should be evaluated by a phantom. Although for mammography, there are several commercial phantoms, for tomographic X-ray phase-contrast imaging systems dedicated to breast screening, they are absent. Therefore, this study aimed to design a breast phantom for application in phase-contrast computed tomography (PC-CT) imaging.
A breast phantom dedicated to X-ray phase-contrast imaging was designed. The phantom has a cylindrical shape and is composed by PMMA, to mimic the breast of a young woman, with some inserts filled with tissue substitutes to normal and pathological breast tissues, such as ethanol and glycerol. These materials were chosen due to the similarity in the attenuation and scattering properties of normal and pathological human breast tissues.
A comparison between tomographic X-ray absorption imaging and tomographic X-ray phase-contrast imaging showed a significant increase in edges definition, even with materials with similar attenuation properties.
The results of this work reinforce the need for dedicated phantoms to exploit the features of each imaging modality more realistic. In particular, the breast phantom–designed breast screening by PC-CT allows exploiting the features of this new imaging modality.
KeywordsPhantom X-ray phase contrast Breast cancer
Mammography is the gold clinical standard imaging method to detect breast cancer in humans (Mautner et al. 2000). It is an imaging modality based on the distinct attenuation of the X-ray through the breast tissues. However, mammography has limitations in detecting tumors at the very early stage as well as in young women, mainly due to the small differences (contrast) between the attenuation coefficients of the breast tissues, which reduces the detection efficiency of this exam (Tomal et al. 2010). Thereby, several complementary imaging techniques have been introduced to eliminate these inherent limitations, e.g., ultrasound (Berg et al. 2008), magnetic resonance imaging (Hartman et al. 2004; Morrow et al. 2011), breast tomosynthesis (Niklason et al. 1997), and X-ray phase-contrast imaging (Castelli et al. 2011; Donath et al. 2010).
Among the existing alternatives, X-ray phase-contrast computed tomography (PC-CT) has attracted the interest of researchers (Fernández et al. 2005; Bravin et al. 2007; Conceição et al. 2014; Fiedler et al. 2004; Keyriläinen et al. 2010). Phase-contrast imaging is based on the phase shift on the beam transmitted through the sample (Lewis 2004). The PC-CT images of the breast are incredibly efficient in localizing the tumor and revealing its size and inner structure since the tumor boundary is enhanced. Thereby, clinical implementation of PC-CT has been proposed (Bravin et al. 2013; Castelli et al. 2011; Coan et al. 2013; Stampanoni et al. 2011).
As every imaging modality clinically implemented, the capabilities and limitations of PC-CT should be evaluated by an imaging phantom. Imaging phantoms are objects stable over time that simulate the properties of the organ/tissue under investigation, specially designed for a type of imaging modality. For conventional mammography, ideal phantom materials would represent the attenuation of pure breast fat, fibroglandular tissues, and typical benign and malignant tumors (Byng et al. 1998). Despite well-established phantoms for mammography (Caldwell and Yaffe 1990; Carton et al. 2011; Ikejimba et al. 2017), for PC-CT, there is a lack of suitable phantom designed to evaluate the specific image features of this imaging modality. This fact makes it difficult to exploit the full advantages of a phase-contrast imaging, especially those related to the edge-defining capabilities of the technique. Therefore, this study aimed to design a breast phantom dedicated to X-ray phase-contrast computed tomography imaging.
To design the breast phantom for PC-CT, two essential features were considered: (i) the generated image is three dimensional and (ii) the contrast is based on the phase shift of the emerging beam which is transformed into amplitude modulation. This contrast is superimposed onto the attenuation contrast on the image improving the visibility of the borders of a structure. Regarding the dimensionality of the image, a cylindrical-shape phantom was designed instead of the typical slab phantom for the conventional mammography. Furthermore, the commercial phantoms available for mammography, such as CIRS (CIRS Inc., Norfolk, VA, USA), are commonly made by epoxy resin where just the X-ray attenuation similarities with the breast tissues are taken into account, or mimics a human breast composed of 50% adipose tissue and 50% glandular tissue as the Gammex 156 (Gammex-RMI Middleton, WI, USA). Thereby, bearing in mind the challenge in breast screening to detect a tumor in young women, the composition of the breast phantom for PC-CT designed in this study was chosen to mimic a young breast (extremely dense), besides considering the similarities in X-ray absorption and scattering of fibroglandular, adipose as well as breast carcinoma was chosen to simulate a carcinoma in a young woman. Fibroglandular tissue is composed of glandular and connective (fibrous) tissues. It presents a higher percentage of oxygen than carbon in its composition and is relatively denser than adipose breast tissues. Adipose tissue is composed mainly of specialized cells in storage lipids (adipocytes). It has a higher percentage of carbon than oxygen in its composition and is relatively less dense than the other breast tissues (Antoniassi et al. 2011; Woodard and White 1986). Carcinoma has a chemical composition similar to fibroglandular tissue and is generally denser than that tissue (Poletti et al. 2002). In this way, polymethylmethacrylate (PMMA, C5H8O2) was chosen as simulator of fibroglandular tissue due to the similarity of their linear attenuation (μ) (Tomal et al. 2014) and scattering coefficients (Poletti et al. 2002) as well as be solid at room temperature, which facilitates the insertion of other tissue equivalent materials inside it. Ethanol (C2H6O) was chosen to mimic the adipose tissue because it presents a large mass proportion of carbon in its composition and similar absorption and scattering proprieties to that tissue (Shakeshaft et al. 1997). Finally, glycerol (1,2,3-propantriol-C3H8O3) was used as a breast carcinoma simulator, because of its higher mass proportion of oxygen, which implies higher electron density (Al-Bahri and Spyrou 1998) and, oxygen-oxygen and oxygen-hydrogen intermolecular distribution function (Chelli et al. 1999) similar to those for malignant breast tissue (Antoniassi et al. 2010; Conceição et al. 2011; Cunha et al. 2006) as well as its relatively larger linear attenuation coefficient (Tomal et al. 2010) likewise for breast carcinoma for the energy used in this study.
The PC-CT tomograms were reconstructed by an in-house-developed software (Ribeiro et al. 2011) based on the standard filtered back projection algorithm with Ram-Lak filter. To compare PC-CT images with conventional computed tomography (CT), tomograms of the breast phantom were acquired using the Skyscan 1172 microtomograph with a resolution of 25.6 μm and were reconstructed by the NRecon software from Bruker®. Some post-reconstruction analyzes were performed using the CT-analyzer (CTan) software and the ImageJ® software.
Quantitative features were extracted both from PC-CT and conventional CT. These features were used to evaluate the signal-to-noise ratio for the edge (SNREdge) and visibility (V) (Pagot et al. 2005), calculated as presented in Eqs. (2) and (3). While the SNREdge is related to the ratio between the signal of a given edge over the noise, the visibility (V) is associated with the ability to distinguish between adjacent edges in a sample. The following equations are used to calculate these features:
From Fig. 4, it is possible to observe the similarity of the radiological aspect between the breast tissues in the mammogram and the tissue equivalent material chosen for composing the phantom. As expected, the dark hypodense (radiolucent) region of the image is that composed of ethanol (adipose equivalent tissue) while the lighter radiodense (radiopaque) region is that composed of glycerol (carcinoma equivalent tissue). The region composed of PMMA (fibroglandular equivalent tissue) presents an intermediate radiographic appearance.
Comparing the PC-CT and transmission CT images from Fig. 5 is observed that even with the significant difference in pixel size between the PC-CT (200 μm2) and transmission detector (25 μm2), visually the images present a similar contrast.
SNREdge and visibility (V) values for edges region of the glycerol of transmission CT and phase-contrast PC-CT images
Phase contrast (PC-CT)
It can be seen from Table 1 that SNREdge and visibility present higher values for phase-contrast tomography showing the better ability of this technique in differentiating the edges of the glycerol (carcinoma equivalent tissue). Furthermore, these features highlight the potential of this technique to detect breast tumor in young women, where the breast is composed mainly by fibroglandular tissue that is one the biggest challenge in breast cancer imaging detection.
The breast phantom for phase-contrast computed tomography was designed to exploit the features of this type of 3D imaging method by its cylindrical shape and the materials selected on the basis their X-ray absorption and scattering similarities with normal and tumoral breast tissues. Furthermore, the phantom matrix was made by PMMA to simulate the breast of a young woman, where the sensitivity of the mammography drops as low as 48% for detecting a breast tumor (Berg et al. 2012).
Although mammography provides a two-dimensional image, where the whole volume of the breast is superimposed on a plane, this study focus on the comparison with computed tomography to show that even with a 3D imaging method, the ability to define the tumor boundaries by PC-CT is larger than an absorption contrast imaging such as in CT or mammography. From the comparison between phase contrast (PC-CT) and conventional transmission (CT) tomographic images, the visibility increase by 38.6% while the SNREdge increases to 25.8% in X-ray phase-contrast images compared to conventional CT images.
Finally, we demonstrate the needed for a dedicated breast phantom for X-ray phase-contrast computed tomography imaging to exploit the features of this imaging modality. Shortly, we intend to improve the design of this phantom by adding a sequence of holes diminishing the diameter regularly to assess the resolution as well as including material to simulate benign lesion. Moreover, using an in-line arrangement with a microfocus X-ray laboratory source and a detector on an optical table, we optimize the acquisition, image handling and reconstruction of phase-contrast images. Therefore, it contributes to corroborate the use of phase-contrast imaging for future clinical application in breast cancer screening to overcome the limitation of the current breast imaging methods.
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. In addition, the authors would like to acknowledge the support of the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and of the LACTEC Institute.
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