The diagnostic value of phase-contrast breast CT: from synchrotron to conventional x-ray sources

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1 The diagnostic value of phase-contrast breast CT: from synchrotron to conventional x-ray sources Poster No.: C-2401 Congress: ECR 2013 Type: Scientific Exhibit Authors: S. Grandl 1, M. S. Willner 1, J. Herzen 2, D. Mayr 1, S. Auweter 1, A. Hipp 1, F. Pfeiffer 1, M. F. Reiser 1, K. Hellerhoff 1 ; 1 Munich/DE, 2 Geesthacht/DE Keywords: DOI: Breast, Soft tissues / Skin, CT, Physics, Technical aspects, Pathology /ecr2013/C-2401 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 11

2 Purpose In the last two decades, various X-ray phase-contrast imaging techniques have been developed [1]. An application of this contrast modality in mammography or breast CT might enhance tumor diagnostics due to its improved visualisation of softtissue compared to conventional absorption-based imaging [2-4]. The morphology of abnormalities in the breast and the phase-contrast signal inducing properties of the corresponding tissues are of great importance to evaluate the potential diagnostic benefits and the technological feasibility of phase-contrast imaging. In this study, we demonstrate the possibility of spatially-resolved quantitative breast tissue characterization using X-ray grating interferometry at laboratory X-ray sources. The results shall provide the fundament for further investigations in this field of research. Methods and Materials A detailed description of the phase-contrast imaging technique applied in this study (X-ray grating interferometry) can be found in Weitkamp et al. [5]. A phase grating is used as beam splitter and creates periodic intensity modulations at certain distances, the so-called fractional Talbot distances. Differences in the phase shift that X-rays undergo when passing two adjacent paths through an object cause a local shift of this pattern. Attenuation by the object, on the other hand, results in a loss of intensity as commonly exploited in conventional X-ray imaging. Usually the detector pixel size exceeds the period of the intensity pattern, which typically is in the order of a few microns. For this reason, an analyzer grating of the same period as the interference pattern and with high absorbing structures is placed in front of the detector. This grating is translated perpendicularly to the grating lines while several images are acquired. During this stepping approach, a sinusoidal intensity oscillation is recorded in each detector pixel. Mean intensity and position of this curve can be evaluated by Fourier analysis. A comparison of data obtained with and without sample in the beam finally provides two radiographic images: the conventional attenuation-contrast and the differential phasecontrast image. The basic principle of the method is graphically displayed in Fig. 1 to give a more illustrative idea of the concept. By extending the described setup by a third grating, the method can be operated with laboratory X-ray sources [6]. Page 2 of 11

3 Fig. 1: Principle of a grating-based X-ray interferometer. The phase grating creates a periodic intensity pattern that can be resolved by placing an analyzer grating in front of the detector. A sample in the incident beam causes slight refraction, which results in a local shift of the analyzed pattern. In a tomography scan, many projection images are generated from different angular directions and a 3D-volume of the object can then be reconstructed by applying, e.g., the filtered backprojection algorithm. In case of phase contrast, the filter function in the reconstruction algorithm has to be replaced by an imaginary Hilbert filter to cope with the differential nature of the projections. Taking setup-dependent factors into consideration, the distribution of the linear attenuation coefficient µ (x, y, z) and the refractive index decrement # (x, y, z) within the sample can be determined from the attenuation-contrast and phase-contrast datasets, respectively [7]. Phase-contrast Hounsfield Units (HU-PH) can be defined in analogy to the well-known Hounsfield Units for absorption-based imaging by replacing the attenuation coefficient µ with the corresponding refractive index decrement #: Page 3 of 11

4 Fig. 2: Formula for the calculation of phase-contrast Hounsfield Units [8]. Results Phase-contrast tomography scans of breast specimens using an X-ray grating interferometer have been performed at synchrotron and laboratory X-ray sources. The samples examined in the study contained several tumor types including an invasive ductal carcinoma, a phyllodes tumor, a fibroadenoma and an invasive lobular carcinoma. Different tissue types - adipose tissue, fibrous tissue and tumour tissue - have been quantitatively analysed and were compared to values obtained from literature. Synchrotron source Grating-based phase-contrast tomography scans of a healthy breast specimen (Fig. 3) and a specimen with invasive ductal breast cancer (Fig. 4) have been carried out at an energy of 23 kev at the European synchrotron radiation facility (ESRF) in Grenoble, France. More detailed information on measurements and specimens can be found in Sztrókay et al. [9]. The histograms in Fig. 3 and 4 correspond to cubic regions of 0.5 cm side length. The peak maxima of adipose tissue are between -66 and -68 HU-PH for both specimens. Differences can be observed for healthy fibrous tissue (66 HU-PH, Fig. 3, region B) and tumor tissue (47 HU-PH, Fig. 4, region B). Dilated ducts appear as bright structures within the tumor. Page 4 of 11

5 Fig. 3: Phase-contrast imaging results of a healthy breast specimen and histograms of two cubic regions. Page 5 of 11

6 Fig. 4: Phase-contrast imaging results of an invasive ductal breast cancer and histograms of two cubic regions. Comparison to literature 24 small regions of interest (10x10 pixels) of these synchrotron datasets have been analysed for adipose tissue, healthy fibrous tissue, the invasive tumor and the ductal structures therein to quantitatively assess phase-contrast Hounsfield Units of the given tissue types. They are compared to literature values based on tissue compositions or electron density measurements obtained by Compton scattering methods in Table 1. Inhomogeneities within the examined tissue samples are one of the reasons for the wide variety of values in literature. Page 6 of 11

7 Table 1: Phase-contrast Hounsfield Units measured at the synchrotron compared to values found in literature. Laboratory X-ray source Breast specimens of different tumor types - phyllodes tumor (Fig. 5), fibroadenoma (Fig. 6) and invasive lobular carcinoma (Fig. 7) have been measured at a laboratory X-ray source (Mo, 40 kv) at the Physics Department of TU München in Garching, Germany. The histogram of a cubic region within the phyllodes tumor specimen (Fig. 5) reflects the HU-PH differences of fibrous tissue (66 HU-PH) and tumor tissue (44 HU-PH). The phase-contrast Hounsfield Units of adipose tissue (-67 HU-PH) are consistent with the results obtained at the synchrotron. Phase-contrast Hounsfield Units found for the fibroadenoma specimen (Fig. 6) are around 45 HU-PH as for the other inspected tumor types. Structures with higher values (up to 65 HU-PH) are visible within the fibroadenoma and belong to dilated ducts. One of the most complicated breast tumors in diagnostics is the invasive lobular carcinoma (Fig. 7). The correlation of histology to phase-contrast imaging results indicates a potential differentiation between fibrous collagen-rich tissue (A, ~68 HU-PH) and infiltrated tumor tissue (B, ~52 HU-PH). Page 7 of 11

8 Fig. 5: Histology and phase-contrast images of a phyllodes tumor surrounded by adipose and fibrous tissue. Page 8 of 11

9 Fig. 6: Phase-contrast imaging results of a fibroadenoma. Fig. 7: Histology (HE and EvG staining) of an invasive lobular carcinoma and correlated phase-contrast image. Conclusion There is a good agreement of quantitative tissue values obtained from lab-based and synchrotron measurements. In literature, specific tissue types are not well discriminated/ defined and show a wide variety of corresponding values. Further spatially-resolved quantitative tissue characterization as presented in our study should be performed as the knowledge of reliable tissue properties is essential for realistic simulations in feasibility studies [10], the design of adequate phantoms and the interpretation of mammographic images. Page 9 of 11

10 The results of our examinations at this stage concerning the applicability of phasecontrast breast CT raise two main issues for technologists and radiologists: Is it feasible to realise a dose compatible system that can resolve HU-PH? And can the differentiation between fibrous and less fibrous tissue or the visibility of dilated ducts improve diagnostics? References [1] A. Momose, "Recent advances in X-ray phase imaging," Japanese Journal of Applied Physics 44, (2005). [2] E. Castelli, M. Tonutti, F. Arfelli et al., "Mammography with synchrotron radiation: first clinical experience with phase-detection technique," Radiology 259(3), (2011). [3] M. Stampanoni, Z. Wang, T. Thuring, C. David, E. Roessl, M. Trippel, R.A. Kubik- Huch, G. Singer, M.K. Hohl, and N. Hauser, "The first analysis and clinical evaluation of native breast tissue using differential phase-contrast mammography," Invest. Radiol. 46(12), (2011). [4] Y. Zhao, E. Brun, P. Coan, Z. Huang, A. Sztrókay, P.C. Diemoz, S. Liebhardt, A. Mittone, S. Gasilov, J. Miao, and A. Bravin, "High-resolution, low-dose phase contrast X- ray tomography for 3D diagnosis of human breast cancers," Proc. Natl. Acad. Sci. USA 109(45), (2012). [5] T. Weitkamp, A. Diaz, C. David, F. Pfeiffer, M. Stampanoni, P. Cloetens, and E. Ziegler, "X-ray phase imaging with a grating interferometer," Opt. Express 13, (2005). [6] F. Pfeiffer, T. Weitkamp, O. Bunk, and C. David, "Phase retrieval and differential phase-contrast imaging with low-brilliance X-ray sources," Nature Phys. 2, (2006). [7] J. Herzen, T. Donath, F. Pfeiffer, O. Bunk, C. Padeste, F. Beckmann, A. Schreyer, and C. David, "Quantitative phase-contrast tomography of a liquid phantom using a conventional X-ray tube source," Opt. Express 17, (2009). [8] T. Donath, F. Pfeiffer, O. Bunk, C. Gr unzweig, E. Hempel, S. Popescu, P. Vock, and C. David, "Toward clinical X-ray phase-contrast CT: Demonstration of enhanced softtissue contrast in human specimen," Invest. Radiol. 45, (2010). [9] A. Sztrókay, J. Herzen, S. D. Auweter, S. Liebhardt, D. Mayr, M. Willner, D. Hahn, I. Zanette, T. Weitkamp, K. Hellerhoff, F. Pfeiffer, M. F. Reiser, and F. Bamberg, "Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive Page 10 of 11

11 ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up," Eur. Radiol. 23, (2013). [10] R. Raupach, T. Flohr, "Performance evaluation of X-ray differential phase contrast computed tomography (PCT) with respect to medical imaging," Med. Phys., 39(8), (2012). Personal Information Page 11 of 11