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Radiologist Evaluation of an X-ray Tube-Based Diffraction-Enhanced Imaging Prototype Using Full-Thickness Breast Specimens

Rationale and Objectives

Conventional mammographic image contrast is derived from x-ray absorption, resulting in breast structure visualization due to density gradients that attenuate radiation without distinction between transmitted, scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for increased contrast with decreased radiation dose compared to conventional mammographic imaging because of monochromatic x-rays, its unique refraction-based contrast mechanism, and excellent scatter rejection. However, a lingering drawback to the clinical translation of DEI has been the requirement for synchrotron radiation.

Materials and Methods

The authors’ laboratory developed a DEI prototype (DEI-PR) using a readily available tungsten x-ray tube source and traditional DEI crystal optics, providing soft tissue images at 60 keV. Images of full-thickness human breast tissue specimens were acquired on synchrotron-based DEI (DEI-SR), DEI-PR, and digital mammographic systems. A panel of expert radiologists evaluated lesion feature visibility and correlation with pathology after receiving training on the interpretation of refraction contrast mammographic images.

Results

For mammographic features (mass, calcification), no significant differences were detected between the DEI-SR and DEI-PR systems. Benign lesions were perceived as better seen by radiologists using the DEI-SR system than the DEI-PR system at the [111] reflectivity, with generalizations limited by small sample size. No significant differences between DEI-SR and DEI-PR were detected for any other lesion type (atypical, cancer) at either crystal reflectivity.

Conclusions

Thus, except for benign lesion characterizations, the DEI-PR system’s performance was roughly equivalent to that of the traditional DEI system, demonstrating a significant step toward clinical translation of this modality for breast cancer applications.

Cancer imparts distinct and measurable changes in breast tissue at the cellular level. In conventional, attenuation-based radiography, variations in the density of the breast tissue lead to varied x-ray attenuation and thus varied intensity in the image. Contrast based on the spatial distribution of x-ray attenuation is not always sufficient to distinguish between normal and cancerous tissues. However, additional contrast can be gained from the refraction of x-rays. Microscopic and macroscopic alterations in the breast tissue may cause x-ray refraction, a minute change in the direction of x-ray propagation, which is exploited by phase-contrast imaging. X-ray refraction contrast is not yet widely used in medical imaging, although several phase-contrast imaging devices are in various stages of research and development .

Diffraction-enhanced imaging (DEI) is a specific type of analyzer-based phase-contrast imaging. Traditionally, DEI has used intense, highly collimated synchrotron radiation (SR) to produce images on the basis of absorption, refraction, and extinction contrast . The application of DEI to breast imaging has consistently provided a superior signal-to-noise ratio (contrast) compared to conventional radiographic images .

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Materials and methods

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Specimen Selection

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Figure 1, Specimen mounting. The specimens were sliced as per usual clinical practice prior to inclusion in the current study. The slices were realigned, and care was taken to eliminate air bubbles from the tissue layers before mounting the specimen with deionized water in the container with mild compression to prevent movement.

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DEI

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Figure 2, Synchrotron-based diffraction-enhanced imaging (DEI-SR) and prototype DEI (DEI-PR) configurations. (a) Traditional DEI-SR configuration, which implements a synchrotron source. (b) DEI-PR setup, with two significant modifications from the traditional system. First, the x-ray source is a commercially available tabletop x-ray tube. Second, DEI-PR uses a single-crystal monochromator instead of the traditional double-crystal monochromator.

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Full-field Digital Mammography

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Pathologic Correlation

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Flux, Dose, and Signal Measured at the Detector

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Table 1

Specimen Radiographic Density

Specimen Percentage Density Glandular Thickness (cm) Adipose Thickness (cm) 1 20% 1.35 5.40 2 30% 2.55 5.95 3 20% 1.70 6.80 4 50% 2.25 2.25 5 30% 2.55 5.95 6 30% 2.55 5.95

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Reader Study

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Statistical Methods

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Results

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Figure 3, Comparison of benign lesion characteristic visibility. This specimen (12.5 × 17.5 cm) contains a circled region of interest, which represents dense stromal sclerosis, a biopsy cavity, fibrocystic change, and focal atypical ductal hyperplasia with associated calcifications. (a) Digital mammographic standard, acquired at 22 keV. Diffraction-enhanced images (b–e) were acquired at 60 keV using the [333] reflectivity. Synchrotron-based diffraction-enhanced images are displayed in the first column , and prototype diffraction-enhanced images are shown in the second column . The top row in (b) and (c) displays the +0.5 Darwin width ( W D ) rocking-curve position, and the bottom row in (d) and (e) displays the −0.5 W D rocking-curve position.

Figure 4, Comparison of malignant lesion characteristic visibility. The magnified views of this region of interest (approximately 6.5 × 5 cm) represent apocrine-type ductal carcinoma in situ (nuclear grade 2–3 with necrosis without associated calcifications), proliferative fibrocystic change, and duct ectasia. (a) Digital mammographic standard, acquired at 29 keV. Diffraction-enhanced images (b–e) were acquired at 60 keV using the [333] reflectivity. The first column (b,c) was acquired using synchrotron-based diffraction-enhanced imaging (DEI), and the second column (e,d) was acquired using prototype DEI. The top row in (b) and (e) displays the +0.5 Darwin width ( W D ) rocking-curve position, and the bottom row in (c) and (d) displays the −0.5 W D rocking-curve position.

Figure 5, Effect of crystal reflectivity on lesion feature visibility. This magnified region of interest (approximately 3.5 × 4.5 cm) contains duct ectasia, proliferative fibrocystic change, stromal sclerosis, and calcifications at pathologic analysis. The digital mammographic image is displayed in (a) , and (b) through (d) show the region of interest acquired on the synchrotron-based diffraction-enhanced imaging (DEI-SR) system at the [333] reflectivity at the +0.5 Darwin width ( W D ), −0.5 W D , and peak rocking-curve positions, respectively. (e–g) Same region of interest and rocking-curve positions acquired using the DEI-SR system at the [111] reflectivity.

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Figure 6, Reader study analysis of radiographic feature visibility. Three expert radiologists ranked radiographic feature visibility on a scale ranging from 1 (not easily appreciated) to 5 (easily appreciated). These scores were averaged for all masslike and calcification regions of interest as perceived on the synchrotron-based diffraction-enhanced imaging (DEI-SR), prototype DEI (DEI-PR), and digital mammographic (DM) systems. Average scores obtained for images acquired at the [333] reflectivity (left) and the [111] reflectivity (right) are shown.

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Table 2

Reader Study Analysis of DEI Correlation with Pathologic Findings

DEI-SR DEI-PR Reflectivity Pathologic Feature_n_ Mean SD_n_ Mean SD_P_ 333 Benign 17 1.84 0.35 9 1.94 0.74 .8294 Atypical 9 1.87 0.43 6 2.03 0.51 .4367 Malignant 11 1.94 0.47 7 1.88 0.48 .5465 111 Benign 18 2.05 0.38 4 1.46 0.25 .0003 Atypical 6 2.06 0.69 4 2.03 0.37 .9061 Malignant 18 2.92 0.89 — — — —

DEI, Diffraction-enhanced imaging; DEI-PR, prototype DEI; DEI-SR, synchrotron-based DEI; SD, standard deviation.

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Discussion

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Acknowledgments

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