Simulation and Phantom Studies of Contrast-Enhanced Dual Energy Mammography (CEDEM) Shih-Ying Huang1,2, John M. Boone1,2, Dandan Zheng3, Kai Yang1,2, Nathan J. Packard1,2, and George Burkett Jr.2 1
Department of Biomedical Engineering, University of California, Davis, Genome and Biomedical Sciences Building - 451 East Health Sciences Drive, Davis, CA 95616 2 Department of Radiology, University of California, Davis, X-ray Imaging Laboratory, U.C. Davis Medical Center, 4701 X Street, Sacramento, CA 95817 3 Department of Radiation Oncology, Virginia Commonwealth University, 401 College Street, Richmond, VA 23298
[email protected]
Abstract. Contrast-enhanced dual energy mammography (CEDEM) has been shown effective in enhancing the visibility of breast cancer in diagnostic mammographic images. The simulation and phantom studies of CEDEM were implemented to enhance acquisition techniques of a dedicated cone-beam breast CT scanner fabricated in our laboratory. CEDEM images were computersimulated numerically, and the results were compared and validated with physical experiments using a custom-made breast-equivalent phantom with pseudo anatomical structures. The technique factors to be optimized included low- and high-energy x-ray spectra (kVp), spectra filters and mAs (x-ray tube current × scan time in second). Signal-difference-to-noise ratio (SDNR) of the logweighted subtracted image was computed to optimize subtraction parameters using several combinations of breast compositions and thicknesses. Both simulation and phantom studies suggest that 40 kVp (filtered with 1.5 mm Al) and 50 kVp (filtered with 1.5 mm Al and 0.3 mm Cu) were the optimal spectra with the highest SDNR on the dual energy subtracted image of a 6-cm, 50% glandular breast. Breast composition and thickness were found to have little influence on the optimized technique factors. We conclude that the simulation and phantom studies demonstrated the effectiveness of CEDEM using the prototype breast CT scanner in producing high-quality, lesion-enhanced images. Keywords: contrast-enhanced dual energy mammography, computer simulation, anatomical breast phantom.
1 Introduction Promising lesion enhancement with contrast agent has been demonstrated in several modalities, including dual energy mammography1 and breast MRI2 (typically with the injection of gadolinium contrast agent). The leaky vasculature at a tumor site contributes to the contrast agent build up in the surrounding tissue. We believe that contrast-enhanced dual-energy mammography (CEDEM) can capture tumor-enhanced E.A. Krupinski (Ed.): IWDM 2008, LNCS 5116, pp. 124–129, 2008. © Springer-Verlag Berlin Heidelberg 2008
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images as a cost-effective substitute for breast MRI with potentially equivalent diagnostic performance. It may serve as a fast and low-dose acquisition technique to depict the kinetic curve in breast carcinoma, and could be used in concert with a contrast-enhanced breast CT acquisition.
2 Methods and Materials Computer simulation of the CEDEM system was implemented using a numerical approach tailored to the scanner geometry of the prototype breast CT scanner. In this study, anatomical structures (instead of homogeneous distribution of breast tissue) were randomly distributed in the simulated phantom as well as the static physical phantom. The numerical simulation was implemented in C (Microsoft VC++ 6.0 SP 5, Redmond, WA). The simulated dual-energy images were generated using the following steps: (1) tungsten-anode x-ray spectral models were generated by TASMIP3(Tungsten Anode Spectral Model using Interpolating Polynomials) (2) threedimensional voxelized phantoms with glandular-tissue filled spheres and iodine reservoir were modeled (3) Poisson-distributed quantum noise was added, and (4) the mean glandular dose (MGD) was evaluated. The delivered MGD, equivalent to a single-view mammogram, was adjusted for breast thicknesses in simulation and phantom studies. Numerical simulations were performed with the kVp range of 40 – 145 kVp (5 kVp interval) with fifteen permutations of breast phantoms (2, 4, 6, 8, 10-cm thick; 25, 50, 75% glandular). In both simulations and experiments, 1.5-mm Al was added to all x-ray spectra while an additional 0.3-mm Cu was used only for high-energy images. Subsequent to dual-energy image generation, weighted logarithmic subtraction was implemented using Eq. 1:
I DE (x, y ) = ln I L ( x, y ) − wt ln I H ( x, y )
(1)
The signal-difference-to-noise ratio (SDNR) of the subtracted image was also evaluated (Eq. 2):
SDNR =
sc − sbg
σ c2 + σ bg2
(2)
where s and σ are the grey-scale mean and variance; the subscript c denotes the contrast region of interest (ROI) corresponding to a specific iodine concentration and bg denotes the non-contrast ROI. The optimized wt was the weighting factor that produced the maximum SDNR on the subtracted image. In addition, a series of breast-equivalent phantoms were fabricated to evaluate the effectiveness of CEDEM experimentally. Water was used to mimic breast glandular tissue while polyethylene was used to model adipose tissue due to their similar x-ray transmission properties. Similar to the phantom modeled in the numerical simulations, pseudo anatomical structures were constructed approximating the tissue distribution of a real breast by creating holes on the polyethylene slabs. 2
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The iodine-based contrast solution (320 mg/ml iodixanol, VisipaqueTM) was diluted to several concentrations and filled in rectangular cells (4.5 × 1.0 × 1.0 cm3 cuvettes, Ocean Optics, Dunedin, FL). In constructing a 6-cm, 40% glandular breast phantom, a number of the custom-made polyethylene slabs were inserted in a sealed container filled with water. For the purpose of the CEDEM study, 7.6-cm and 9.6cm breast-equivalent phantoms were also fabricated with the same method. Slightly thicker breasts were modeled since lighter compression will be applied to the breast in this application compared to mammography. A series of projection images (using 1 × 1 low gain detector mode) were acquired with the custom-made phantoms at the scanner isocenter while the scanner gantry was stationary. Acquired images were offset and flat-field corrected, and weighted-log subtraction (Eq. 1) was conducted. SDNR of the subtracted image was evaluated to optimize the subtraction weighting factor (wt). The computer simulation variables were validated in the experimental setting.
3 Results Figure 1 illustrates that the low/high x-ray spectra combination of 40/45-50 kVp demonstrated the highest subtracted image SDNR with all simulated breast phantoms. It also shows that the physical experiments confirmed the simulation result with the optimal spectra combination of 40/50-kVp. Maximum SDNR was observed with approximately 1:1 ratio of dose delivered to the low- and high-energy image among the simulated and experimental phantoms of different thicknesses and composition (6, 7.6, 9.6 cm; 25, 50, 75% glandular). The simulation and experiment results suggested a small effect of breast composition on the magnitude of contrast enhancement, where 25% glandular breast yielded slight higher subtracted image SDNR than 50% and 75% glandular breasts. The reduced anatomical complexity in the less dense breast likely improves the contrast enhancement seen in the subtracted image. Figure 2(a) demonstrates that the optimized SDNR of a simulated 50% glandular breast is independent of breast thickness due to dose compensation. However, Figure 2(b) shows that the experimental subtracted image SDNR did not demonstrate that a change in dose allocation between the two energy images was necessary for different phantom thickness, as shown in the computer simulation. The contribution of detector electronic noise was speculated to be the cause of this trend in the experiment data. Figure 3 illustrates the relationship between the optimized SDNR and the iodine projected thickness (mg/cm2) when a 6-cm, 40% glandular breast was imaged experimentally (40/50 kVp). The data was described by a 2nd-order polynomial (R2 = 0.9993) with the curvature likely due to x-ray beam hardening effect observed in the higher iodine concentrations. The iodine projected thickness of 22.1 mg/cm2 was estimated from the contrast-enhanced breast CT images produced in clinical trial. At 22.1 mg/cm2, significant contrast enhancement (SDNR = 16.4) was observed in the experimental study. This finding suggested the feasibility of the CEDEM technique in a clinical setting, which is the ultimate goal of this research.
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(a)
(b) Fig. 1. The effect of x-ray spectra combinations on the subtracted image SDNR (6-cm, 40%glandular breast optimized with 4 mGy total MGD, SDNRs were computed within a ROI with the iodine concentration of 25.6 mg/ml) using (a) computer simulations (b) experiment validation
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(a)
(b) Fig. 2. The effect of breast thickness on the optimized SDNR from the subtracted image as a function of MGD distribution (between the low- and high-energy acquisitions) on a 40%glandular breast using (a) computer simulations (b) experiment validation
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Fig. 3. A 2nd-order polynomial relationship between the subtracted image SDNR and iodine projected thickness is illustrated. Acquisitions were made with a 6-cm, 40%-glandular breast phantom at 40/50 kVp. The iodine projected thickness was analyzed from a contrast-enhanced bCT image shown on the right corner.
4 Discussion The experimental investigation of CEDEM with a static phantom has shown potential in improving the lesion visibility with the prototype breast CT scanner. Although trends in the experiment results mostly followed that of computer simulation, the utility of the optimized x-ray technique will be further examined considering detector limitations and patient dose issues. A more sophisticated model will be used in the future computer simulations to resolve the discrepancy seen between the simulation and phantom studies. Results of the improved computer simulation scheme will be presented at the conference in details. Furthermore, the clinical function of CEDEM will be evaluated using a dynamic breast phantom which is designed to simulate the kinetics of the “leaky” vessels near the tumor site.
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