Threshold Detectable Calcification Diameter In2d-Mammography and DBT

The effect of system geometry and dose on the threshold detectable calcification diameter in2D-mammography and digital breast tomosynthesis

SHORT TITLE

Threshold detectable calcification diameter in2D-mammography and DBT

AUTHORS

AndriaHadjipanteli1*, Premkumar Elangovan2, Alistair Mackenzie1, Padraig T Looney1, Kevin Wells2, David R Dance1,3 , Kenneth C Young1,3

1National Coordinating Centre for the Physics of Mammography, Royal Surrey County Hospital, Guildford, Surrey, UK.

2Centre for Vision, Speech and Signal Processing, University of Surrey, Guildford, UK.

3Department of Physics, University of Surrey, Guildford, UK.

*Corresponding author: .

ABSTRACT

Digital breast tomosynthesis (DBT) is under consideration to replace or to be used in combination with 2D-mammography in breast screening in the United Kingdom. Different DBT geometries should be compared witheach other and with 2D-mammography in terms of their detectability of cancer. The effect of system doseon cancerdetectability should also be investigated. The aim of this study was thecomparison of the detection of one type of breast cancer (microcalcification clusters) by human observers in breast images using 2D-mammography,narrow angle(15/15 projections) andwide angle(50/25 projections) DBT. The effect of imaging geometry on calcification detection was tested for different positions of the microcalcification cluster in the breast. The effect of three dose levels on calcification detection was also studied. Simulated images of 6 cm thick compressed breasts were produced with and without microcalcification clustersinserted, using a set of image modelling tools for 2D-mammography and DBT. Image processing and reconstruction wereperformedusingcommercial software. A series of 4-alternative forced choice (4AFC) experiments was conducted for signal detection with the microcalcification clusters as targets. Threshold detectable calcification diameter was found for each imaging modality with standard dose:2D-mammography (164±5 μm),narrow angleDBT (210±5 μm) and wide angle DBT (255±4 μm).Statistically significantdifferences were found when using different doses, butdifferent geometries had a greater effect. No differences were foundbetween the threshold detectable calcification diameters when at different heights in the breast. The 4AFC results were correlated with threshold diameters obtained using the CDMAM test phantom at different doses, showing that the CDMAM measurements provide a measure of performance, which is relevant to calcification detection.

1.Introduction and background

Digital breast tomosynthesis (DBT) involves the acquisition of two-dimensional X-ray projections over a limited angular range and their reconstruction to image planes parallel to the detector (Sechopouloset al2013a, Sechopoulos et al 2013b).DBT is currently under consideration and study for its usein combination or alone with 2D-mammography in breast cancer screening in the United Kingdom.For DBT to be combined with 2D-mammography in breast screening it would require the additional dose due to DBT to be justified in terms of mortality and morbidity. For DBT to replace 2D-mammography in screening it would have to at least provide the same detectability of cancer lesions with 2D-mammography, at similar dose levels.

The detectability of a lesion in the breastusing X-ray imaging depends onthe image acquisition methods, dose, image processing, reconstruction algorithms,the physical properties of thebreast and lesion itself. It has already been shown that DBT increases the detectability of masses in the breast and reduces recalls, when used in combination with 2D-mammography (Rafferty et al 2013). Also, DBT alone was shown to perform better in mass detection than 2D-mammography (Elangovan et al 2015). Masses do not have a high contrast in comparison with the healthy breast tissue when 2D-projected, and can thus be superimposed by surrounding structures. DBT separates overlying structures into planesthus decreasing the effect of masses being superimposed on healthy breast tissue.Microcalcifications have a higher contrast in comparison with the healthy breast tissue, but due to their small size (0.26 mmaverage calcification diameter for the real calcifications) (Warren et al 2014), their visualisation can behighlydependent on the resolution of the imaging system. Some studies have shown that the detectability of microcalcifications with DBT is slightly lower than with 2D-mammography, whereas others have claimed that the converse is true (Spangler et al 2011, Kopans et al 2011). It is still unclear whether the detectability of microcalcification clusters in DBT can be as high as that in 2D-mammography.

Image acquisition parameters that are expected to affect the detectability of lesions in DBT include the tomographic scan angular range and the number of projections (which form part of the system geometry) and the breast dose.By increasing the DBT scanangular range, depth resolution increases (Hu et al 2008). However, by increasing the angular range the movement required by the X-ray tube may increase and,unless the system is step-and-shoot (Shaheen et al 2011), blurring can be introduced due to tube motion and the oblique incidence angle (Mainprize et al2006). Wider scan angles need more projections foran adequatesampling of image data and fewer tomosynthesis reconstruction artefacts. However,at a fixed dose, the relative quantum noise will increase in the projection image with the number of projections increasing.In combination with insufficient angular sampling, the quantum noise can have an effect on the detectability of small-scale signals (Reiser et al 2010). Also, electronic noise may become more dominant. Sechopoulos et alhave shown that increasing the number of projectionsdecreases the contrast to noise ratio for microcalcification-like objects (Sechopouloset al2009).

Anoptimum solution should be sought where the angle and number of projections provide a combination of low blurring and low relative noise, for the highest possible detectability of microcalcifications, at a particular dose level. The establishment of the optimum combination of these variables for DBT is complicated, due to the large number of variables. The optimum angle and number of projections for microcalcification detectionreported from different studies varies and seems to be dependent on the study methods, system characteristics (noise levels, blurring levels), dose, imaging conditions, reconstruction methods used, imaging parameters investigated and performance metrics employed (Reiser et al 2009, Sechopoulos et al 2009, Tucker et al 2013,Chan et al 2014, Peterson et al 2015).

Decreasing dose for a fixed geometryincreases the relative noise in an image, creating mainly quantum noise-limited images and will lead to a decrease in the detectability of microcalcifications.Previous studiesthat haveinvestigated the effect of dose on cluster detection include, for 2D-mammography,Warren et al(2012)and Samei et al(2013) and for DBT Timberg et al(2015). All three studies have shown a decrease in diagnostic performance with decreasing dose.

For the investigation of the effect of factors like system geometry and dose on the detectability of lesions, the methods to be used require settings as similar as possible to the clinical case. Ideally, a direct comparison of different systems in a clinical environment would be used. However, this can be time consuming andexpensive.Furthermore, when using high doses, real images would be ethically difficult or impossible to acquire. In this study we use simulation methods to study the detectability of microcalcification clusters by 2D-mammography and DBT. To the best of our knowledge, no study to date has made a quantitative measurement of the threshold diameter required for microcalcification detection, using high resolution, realistic images with observers, for the comparison of DBT geometries with 2D-mammography. The methods used in this study (Elangovan et al 2014) satisfy these requirements.They involve the realistic simulation of breast images with calcification clusters and their use in 4-alternative forced choice (4-AFC) observer studies.The values of the threshold detectable calcification diameter determined from the observer studies were then compared for each modality and imaging conditions investigated. Using this approach we compared the performance of 2D-mammography, narrow angle DBT and wide angle DBT for microcalcification cluster detection. We also studied the influence of the height of the cluster above the breast support and breast dose on this detection task.

Finally, the threshold detectable calcification diameters from the observer studies were correlated with the threshold diameters obtainedat different dose levels using the CDMAM mammography test object (Artinis Medical System, Zetten, The Netherlands), the standard European method of measuring 2D mammographic image quality (van Engen et al2003). It has already been shown that the clinical effectiveness of four available 2D-mammography systems in detecting calcification clusters is linked to image quality assessment using the CDMAM phantom (Mackenzie et al 2016). The European protocol for the quality control of the physics and technical aspects of DBT(van Engen et al 2015) recommends some limited use of it in the DBT, for example, in assessing the stability of image quality. However, it is currently unknown how the results obtained using the CDMAM test object relate to the clinical performance of both 2D-mammography and DBT at different dose levels.

2. Methods and Materials

In this investigation the microcalcification detection performance of 2D-mammography and two DBT systems has been compared using simulated images and a series of 4-AFC observer studies. The simulation involved three stages: creation of voxel phantoms of the breast, creation of simulated calcification clusters into the phantom, and calculation of images. These stages, together with the 4-AFC methodology and analysis, and the correlation of the results to CDMAM results are described in sections 2.1-2.6below.

Two comparative performance studies were performed, as detailed in table 1. In arm 1 of the study the effect of system geometry and cluster insertion height above the breast support on microcalcification detection were tested, while keeping dose constant between the systems. In arm 2 the effect of dose was investigated for the three different geometries, and the cluster insertion height was kept constant. In all cases, the breast glandularity, breast thickness, cluster diameter and the processing and reconstruction methods were kept constant.

Table 1: Details of variables and constants used in each study arm.

Arm 1 / Arm2
Variables / Geometry / Insertion Height (cm) / Geometry / Mean glandular dose(mGy)
2D-mammography / 1 / 2D-mammography / 1.25
Narrow angle DBT / 3 / Narrow angle DBT / 2.50
Wide angle DBT / 5 / 5.00
Constants / Mean glandular dose (2.5 mGy)
Breast glandularity
Breast thickness
Cluster diameter
Processing and reconstruction methods / Insertion height (3 cm)
Breast glandularity
Breast thickness
Cluster diameter
Processing and reconstruction methods

2.1.Mathematical breast phantom

Realistic mathematical breast phantoms were created using a method described by Elangovan et al (2016). As this study discussed, radiologists found it difficult to distinguish between segments of image of the phantom and real mammograms.A variety of breast tissue structures were first extracted from reconstructed DBT planes of real patient images. The extracted structures were de-noised using a series of morphological image operations. These structures were then scaled and inserted into an empty breast phantom volume containing only adipose tissue. At the end of the simulation process,each phantom was composed of five different tissue types: skin, glandular tissue, adipose, Cooper’s ligaments and blood vessels. The phantomshad a voxel size 100 μm100 μm100 μm.

Each breast phantomproduced had compressed breast thickness 6 cm. The glandularity of each breast phantom was set between 17% and 19% by volume. This glandularity was chosen as it matches the average glandularityof 21% by mass in the centralportion of the breast for women of age 50 to 64 (Dance et al 2000).

2.2. Simulated clusters

Simulated volumesof clusters composed of five microcalcifications were produced. The detection of five microcalcifications in a cluster was regarded as a more realistic representation of the clinical task than detecting a single microcalcification.One high resolution microcalcification image volume was chosen from a database of 400 real microcalcification image volumes (breast biopsy samples), which were acquired using a microcomputed tomography system (Shaheen et al2011). The selected microcalcification was chosen due to its approximately round shape.

Each calcification was assumed to be calcium oxalate, but with an attenuation coefficientset as the product of the attenuation coefficient of calcium oxalate and the factor 0.84. This corrects for differences in the attenuation of calcium oxalate of real calcifications (Warren et al 2013).

The selected microcalcification was replicated five times, but rotated at a different orientation each time and randomly placed within a 2.5 2.5 2.5 mm3 cubic volume. This formed one cluster. There was no overlap between any of the five microcalcifications in the planar projection of the cluster. The above process was repeated to produce 15 different microcalcification clusters. The clusters themselves were then rotated by 90º, 180º and 270º, resulting in 60 different clusters that could be subsequently inserted into the simulated images. All clusters had the same volume (a 2.5 2.5 2.5 mm3), therefore only the microcalcification size, and not the cluster size (the spread of the calcifications), had an effect on the detectability.

The same 60 clusters were then regeneratedwith different calcification sizes. The volume of the cluster was kept the same, while the microcalcifications were scaled to a series of diameters in the range 110μmto 275 μm (section 2.3). Figure 1 shows examples of the microcalcification clusters produced, with two microcalcification diameters: (a) 125 μm and (b) 250 μm.

The microcalcification clusters were inserted into the breast phantoms by voxel replacement. Since the voxel size of the phantoms were much larger than the microcalcification clusters, in the interest of execution time and memory, a slightly different approach was undertaken to avoid super sampling the entire phantom to match the resolution of the microcalcification clusters. A cubic region around the insertion site was represented at high resolution by super sampling the background tissue voxels of the phantom to accommodate the microcalcification clusters without loss of information.

The microcalcification clusters were inserted into themathematical phantoms at three heights above the breast support: 1 cm (arm 1), 3 cm (arms 1 and 2) and 5 cm (arm 1). They were positioned so that a range of positions in the reconstructed image planes was simulated.

(a)(b)

Figure 1. 2D projection images of (2.5 2.5 2.5 mm3 cubic volume) clusters with two different microcalcification diameters before insertion: (a) 125 μm and (b) 250 μm.

2.3. Image Simulation

The image modelling tools developed and validated by Elangovan et al (2014)were used to calculate simulated images of the breast phantom for 2D-mammography and DBT.Together with the mathematical breast and cluster phantoms described above simulated breast images with and without inserted clusters were produced.

A clinically used detector made of amorphous selenium was simulated for both 2D-mammography and DBT. The physical pixel pitch of the detector was set at 0.07 mm, but for narrow and wide angle DBT pixel binning was performed before reconstruction (giving a pixel size of 0.14 mm). The 2D-mammography geometry was based on a clinically existing geometry (Hologic Selenia Dimensions), with a 0.04  0.04 mm2 focal spot size and source to detectordistance of 70 cm.

The narrow angle DBT geometry tested used a 15/15 projections configuration, based on theexisting commercial DBT geometry of Hologic Selenia Dimensions. The wide angle DBT geometry tested used a 50/25 projections configuration,also based on an existing commercial geometry (Siemens Mammomat Inspiration). However for this case only the angle, number of projections and source movement blurring (see below) matched thecommercial system. The rest of the system properties, including the pixel size, detector characteristics and imaging conditions, matched those for narrow angle DBT. The purpose of the first arm of the study was to test the effect of imaging geometry on calcification detectability. It was beyond the scope of the study to compare clinically used systems.

Both DBT systems had a“continuous” and not a “step-and-shoot” configuration.In the “continuous” configuration the source movement introduces blurring, and this effect was incorporated by increasing the focal spot size in the direction of movement in the simulation model. Based on physical measurements of the tube rotation speed and the time of exposure for each projection, made on a Hologic Selenia Dimensions system, for the exposure of a 6 cm thick average breast, the focal spot sizelength(in the direction of tube movement) was found tobe0.14 mm for the narrow angle DBT and 0.22 mm for wide angle DBT. The focal spot size width (in the direction perpendicular to the movement of the tube) was set to 0.04 mm, again based on physical measurements. The focal spot size width and length for 2D-mammography were both set to 0.04 mm. The focal spot size was set as above for both arms of the study.

The kVp and target/filter materials used in the x-ray simulation were: (i) 2D-mammography: 31 kVp W/Rh; (ii) DBT: 33 kVp W/Al; which are typical of those used clinically (Automatic Exposure Control) for a 6 cm thick compressed breast on a Hologic Selenia Dimensions system. The primary images/projections were produced using a tracing tool developed for 2D-mammography and DBT (Elangovan et al 2014), which is based on the Siddon algorithm (Siddon et al 1984). The breast phantom and the high resolution cube containing microcalcification clusters were ray traced separately at 35 μm and 12 μm to 35 μm (depending on the size of the calcificiation) respectively, and the images were stitched together to produce the final image. The spectra used (Boone et al1997) were attenuated by an aluminium thicknessthat was used to match the calculated and measured half value layers (HVL).

For each spectrum, the incident air kerma was calculated and the mean glandular dose (MGD) was computed using data from Dance et al(2000) and Dance et al(2011). Then the spectrum was scaled to achieve the required MGD in the simulations. When investigating the effect of geometry and the height of lesion insertion on calcification detectability (Table 1, arm 1) the MGD was fixed at 2.5 mGy for all three modalities. This dose is used clinically for 2D-mammgraphy and DBT for this breast thickness (Bouwman et al 2015). When testing the effect of dose on calcification detectability in 2D-mammography and narrow angle DBT (Table 1, arm 2)three MGD levels were used: 1.25 mGy, 2.5 mGy and 5 mGy.