Measurement of Tumor Extent and Effects of Breast Compression in Digital Mammography and Breast Tomosynthesis

Breast cancer is the most common form of cancer affecting women in the western countries. Today x-ray digital mammography (DM) of the breast is commonly used for early detection of breast cancer. However, the sensitivity of mammography is limited, mainly due to the fact that a 3D volume is projected down to a 2D image. This problem can be partially solved by a tomographic technique. Breast tomosynthesis (BT) reduces the detrimental effect of the projected anatomy. Tumor size is an important predictor of prognosis and treatment effect. We hypothesized that the tumor outline would be better defined in BT and therefore tumor measurement in BT would be more accurate compared with DM. The results showed that breast tumor size measured on BT correlated better with the size measured by the pathologists on the surgical specimens compared with measurement on DM. Breast compression is important in mammography both to improve image quality and to reduce the radiation dose to the breast, but it also has a negative consequence as some women refrain from mammography due to the pain associated with the examination. Since BT is a 3D technique, it was hypothesized that less breast compression force can be applied. The results indicated that less compression force is possible without significantly compromising the diagnostic quality of the image and that the patient comfort was improved. An applied breast compression force as used in mammography results in a pressure distribution over the breast. The pressure distribution was assessed using thin pressure sensors attached to the compression plate. The results showed that the pressure distribution was heterogeneous in appearance and varied widely between different breasts. In almost half of the subjects most of the pressure was over the juxtathoracic part of the breast and the pectoral muscle with little or no pressure over the rest of the breast. Another concern regarding breast compression is the question whether the resulting pressure might damage tumors, causing a shedding of malignant cells into the blood system. Peripheral venous blood samples were drawn before and after breast compression and analyzed for circulating tumor cells. The study found no elevated number of circulating cancer cells in peripheral blood after breast compression. Future analysis of samples from veins draining the breast are needed to study if circulating tumor cells are being trapped in the lung capillaries

Complementary analysis of breast cancer using MRI and breast tomosynthesis

The purpose of this work is to explore and quantify physical metrics of breast tumors in both magnetic resonance imaging (MRI) and breast tomosynthesis (BT) images, and relate these metrics to patho-physiological and histopathological bindings. An analysis of breast specimens containing tumors will be employed to determine BT metrics of interest. These metrics will then be applied to patient images to test whether they are suitable in predicting malignancy or not. Clinical images of 10 patients who have undergone both MRI and BT examinations have been obtained and studied in this project. The tumors seen in the tomosynthesis slices were characterized by objective measures such as degree of spiculation, irregularity and size. These measures were compared to contrast uptake curves created from the respective tumors in the MR images. Two different MRI methods (wash-in/wash-out and persistent curve type percentage) were established and compared. Both methods have a sensitivity of 100% but the specicity is higher for the persistent curve type percentagemethod. With regards to the BT metrics, the parameters irregularity and ellipticity both had a signicant difference between malignant and benign cases. No relationship was observed in the inter-metric analysis of the BT and MRI metrics, however, not enough data was available to draw any conclusions. The results indicate that the BT parameters irregularity and ellipticity may be useful for differentiation on between malignant and benign tumors.Bröstcancer är den vanligaste cancertypen hos kvinnor i Sverige. Nästan 7000 drabbas och ungefär 1600 avlider årligen som en följd av bröstcancer. Sedan man började med regelbundna hälsoundersökningar med mammografi (så kallad ”screening”) har dödligheten minskat betydligt. Vid konventionell mammografi tas tvådimensionella (2D) röntgenbilder av bröstet. Detta generar en bild som avspeglar röntgenstrålningens penetration genom hela bröstet. I och med att all vävnad i bröstet påverkar penetrationen kan överliggande och underliggande vävnad inte skiljas åt i de framtagna 2D-bilderna. Detta problem försvårar upptäckten av bröstcancer. Nyligen har en metod utvecklats som kan ta tredimensionella (3D) bilder av bröstet. Metoden kallas digital tomosyntes och syftar på att man tar flera bilder av bröstet från olika vinklar med ungefär samma totala stråldos som vid en 2D-undersökning. Med hjälp av ett avancerat datorprogram kan man sedan få fram en 3D-bild av bröstet. En annan teknik som används som ett komplement till mammografi är magnetresonanstomografi med kontrast (MR-kontrast). MR-kontrast grundar sig på förekomsten av nybildade kärl i tumören som suger åt sig den tillsatta kontrasten och skapar en bild av tumörens fysiologi och inte anatomi, som röntgenbaserade tekniker avbildar. Denna metod är bra på att upptäcka tumörer, men är dyr och undersökningarna tar lång tid. I det här arbetet kommer olika mått på tumörer i MR-kontrast och tomosyntesbilder att jämföras och knytas till patologin (sjukdomen). Tumörmassorna i tomosyntesbilderna kommer att karakteriseras av mått som avser tumörens storlek, oregelbundenhet och stråkighet, som kommer att jämföras med kontrastuppladdningskurvor (hur kontrasten sugs upp i tumören under en viss tidsperiod) för respektive tumör i MR-kontrastbilderna. De nämnda tomosyntesmåtten har tagits fram med hjälp av ett datorprogram genom att man först markerar ut tumörernas kanter i bilderna och sedan använder olika datorfunktioner för att beräkna måtten. Måtten är definierade matematiskt och funktionerna kan vara att man exempelvis jämför hur mycket stråkigheter man ”huggit” bort från cancern eller hur lik tumören är en ellips (ju mer ellipsoid, desto mindre farlig är den). Kontrastuppladdningskurvorna fås också fram med ett annat datorprogram, där en bildserie visar hur mycket kontrast cancern sugit upp under en viss tid. Jämförs andelen kontrast i cancern för vissa tider kan programmet skapa en kurva. Denna kurva ser typiskt olika ut för farliga och ofarliga cancrar. Resultatet visar att vissa av de här beräknade måtten är bra på att skilja benigna (ofarliga) och maligna (farliga) tumörer

Changes in breast density over serial mammograms : A case-control study

Purpose: In addition to a breast density category, temporal changes in breast density have gained attention as a dynamic breast cancer risk marker. This case-control study aimed to investigate a potential change in breast density preceding tumor development and the relationship of this potential change to prognostic pathological tumor variables. Method: A total of 51 consecutive, eligible-for-analyses, biopsy-proven breast cancers were diagnosed between 1 st of August and 31 st of December 2014 at Skåne University Hospital, Sweden. Mammogram data and patient- and tumor characteristics were retrieved retrospectively from medical charts. Breast density was quantitatively estimated using LIBRA (a free open source software package). The cases were matched for year of birth, number of screening rounds, and date for first and last mammograms with controls from the Malmö Breast Tomosynthesis Screening Trial in a 1:2 ratio, resulting in median time between mammograms of 4.5 (1.3–11.9) years for cases and 4.7 (1.4–11.1) years for controls, averaging approximately three screening rounds (1–6 rounds). Results: We detected a statistically significant difference in breast density change over time, with cases showing an increase in breast density (1.7 %) as compared to controls (-0.3 %) (p = 0.045). We found that in women with breast cancer, older women (≥ 55 years) experienced a higher breast density increase compared to younger women (5.1 % vs. 0.3 %, p = 0.002). Conclusions: There was a statistically significant difference in density change, where women with breast cancer showed an increased density over time, which was particularly evident in women > 55 years of age

Comparison between software volumetric breast density estimates in breast tomosynthesis and digital mammography images in a large public screening cohort

Objectives: To compare software estimates of volumetric breast density (VBD) based on breast tomosynthesis (BT) projections to those based on digital mammography (DM) images in a large screening cohort, the Malmö Breast Tomosynthesis Screening Trial (MBTST). Methods: DM and BT images of 9909 women (enrolled 2010–2015) were retrospectively analysed with prototype software to estimate VBD. Software calculation is based on a physics model of the image acquisition process and incorporates the effect of masking in DM based on accumulated dense tissue areas. VBD (continuously and categorically) was compared between BT [central projection (mediolateral oblique view (MLO)] and two-view DM, and with radiologists’ BI-RADS density 4th ed. scores. Agreement and correlation were investigated with weighted kappa (κ), Spearman’s correlation coefficient (r), and Bland–Altman analysis. Results: There was a high correlation (r = 0.83) between VBD in DM and BT and substantial agreement between the software breast density categories [observed agreement, 61.3% and 84.8%; κ = 0.61 and ĸ = 0.69 for four (a/b/c/d) and two (fat involuted vs. dense) density categories, respectively]. There was moderate agreement between radiologists’ BI-RADS scores and software density categories in DM (ĸ = 0.55) and BT (ĸ = 0.47). Conclusions: In a large public screening setting, we report a substantial agreement between VBD in DM and BT using software with special focus on masking effect. This automated and objective mode of measuring VBD may be of value to radiologists and women when BT is used as the primary breast cancer screening modality. Key Points: • There was a high correlation between continuous volumetric breast density in DM and BT.• There was substantial agreement between software breast density categories (four groups) in DM and BT; with clinically warranted binary software breast density categories, the agreement increased markedly.• There was moderate agreement between radiologists’ BI-RADS scores and software breast density categories in DM and BT

Towards determination of individual glandular dose

Due to variations in amount and distribution of glandular breast tissue among women, the mean glandular dose (MGD) can be a poor measure of the individual glandular dose. Therefore, to improve the basis for risk assessment related to radiation dose from breast X-ray examinations, the distribution should be considered. Breast tomosynthesis (BT) is an imaging technique that may be used as an alternative or complement to standard mammography in breast cancer screening, and it could provide the required 3D-localisation of glandular tissue for estimation of the individual glandular dose. In this study, we investigated the possibility to localize glandular tissue from BT data and use a Monte Carlo simulation routine to estimate the glandular dose for software breast phantoms with different amount and distribution of glandular breast tissue. As an initial evaluation of the method, the local energy absorption in glandular tissue was estimated for seven breast phantoms and the corresponding phantoms recreated from reconstructed BT data. As expected, the normalized glandular dose was found to differ substantially with glandular distribution. This emphasizes the importance of glandular tissue localization for estimation of the individual glandular dose. The results showed good accuracy for estimation of normalized glandular dose using breast phantoms recreated from reconstructed BT image volumes (relative differences between -7.3% and +9.5%). Following this initial study, the method will be evaluated for more phantoms and potentially developed for patient cases. In the future it could become a useful tool in breast dosimetry as a step towards the individual glandular dose

The Effect of Breast Positioning on Breast Compression in Mammography: a Pressure Distribution Perspective

The standard procedure at mammography is to compress the breast in order to improve image quality, better separate tissue components and reduce absorbed dose to the breast. Traditionally, compression guidelines have been based on applied force, rather than actual thickness reduction. Structures such as the pectoral muscle are stiffer than breast tissue and if compressed along with it, as in the MLO-projection, might absorb much of the applied force. This study investigated the difference in compression of breasts before and after they were repositioned to exclude 1 cm of the juxtathoracic part. Twenty-one women were included in the study. The distribution of compression pressure was measured using thin FSR (Force Sensing Resistor) pressure sensors attached to the compression paddle. Breast thickness and compression force were measured by the mammographic device. Compared to standard positioning the repositioned breasts were thinner by 4.4 +/- 2.3 mm (P < 0.001) (from 50.3 mm to 45.9 mm) and had a 12.3 +/- 24.5 cm(2) (P = 0.032) larger area over which pressure was distributed (from 97.6 cm(2) to 109.9 cm(2)), despite less of the breast being included in the projection. This indicates that the inclusion of the pectoral muscle and other juxtathoracic structures in the MLO-projection substantially affects pressure distribution and prevents proper compression of the breast. The results suggest that the exact positioning of the MLO-projection should be carefully evaluated in order to find a balance between breast compression and tissue inclusion

Impact of breast density on diagnostic accuracy in digital breast tomosynthesis versus digital mammography: results from a European screening trial

Abstract Background The diagnostic accuracy of digital breast tomosynthesis (DBT) and digital mammography (DM) in breast cancer screening may vary per breast density subgroup. The purpose of this study was to evaluate which women, based on automatically assessed breast density subgroups, have the greatest benefit of DBT compared with DM in the prospective Malmö Breast Tomosynthesis Screening Trial. Materials and methods The prospective European, Malmö Breast Tomosynthesis Screening Trial (n = 14,848, Jan. 27, 2010–Feb. 13, 2015) compared one-view DBT and two-view DM, with consensus meeting before recall. Breast density was assessed in this secondary analysis with the automatic software Laboratory for Individualized Breast Radiodensity Assessment. DBT and DM’s diagnostic accuracies were compared by breast density quintiles of breast percent density (PD) and absolute dense area (DA) with confidence intervals (CI) and McNemar’s test. The association between breast density and cancer detection was analyzed with logistic regression, adjusted for ages < 55 and ≥ 55 years and previous screening participation. Results In total, 14,730 women (median age: 58 years; inter-quartile range = 16) were included in the analysis. Sensitivity was higher and specificity lower for DBT compared with DM for all density subgroups. The highest breast PD quintile showed the largest difference in sensitivity and specificity at 81.1% (95% CI 65.8–90.5) versus 43.2% (95% CI 28.7–59.1), p < .001 and 95.5% (95% CI 94.7–96.2) versus 97.2% (95% CI 96.6–97.8), p < 0.001, respectively. Breast PD quintile was also positively associated with cancer detected via DBT at odds ratio 1.24 (95% CI 1.09–1.42, p = 0.001). Conclusion Women with the highest breast density had the greatest benefit from digital breast tomosynthesis compared with digital mammography with increased sensitivity at the cost of slightly lower specificity. These results may influence digital breast tomosynthesis’s use in an individualized screening program stratified by, for instance, breast density. Trial registration. Trial registration at https://www.ClinicalTrials.gov : NCT01091545, registered March 24, 2010

Visibility of single spiculations in digital breast tomosynthesis

Purpose: To investigate the visibility of single spiculations in digital breast tomosynthesis (DBT). Method: Simulated spheres (6 mm diameter) with single spiculations were added to projection images acquired on a DBT system (MAMMOMAT Inspiration, Siemens). The spiculations had a cylindrical shape and were randomly, diagonally aligned (at four different positions: +/- pi/4 or +/- 3 pi/4) at a plane parallel to the detector. They were assumed to consist of a fibroglandular tissue composition. The length of the spiculations was 5 mm while the diameter varied (0.12 - 0.28 mm). Reconstructed central slices of the lesion, separated by insertion in fatty or dense breasts (100 images in each), were used in 4-alternative forced choice (4AFC) human observer experiments. Three different reconstructions were used: filtered back projection (FBP) with 1 mm thick slices and a statistical artifact reduction reconstruction (SAR) method generating 1 and 2 mm thick slices. Five readers participated and their task was to locate the spiculation in randomly presented images from the whole image set (4 diameters x 100 images). The percent correct (PC) decision was determined in both fat and dense tissue for all spiculation diameters and reconstructions. Results: At a PC level of 95% the required diameter was about 0.17 - 0.22 mm in dense tissue, and 0.18 - 0.26 mm in fatty tissue (depending upon reconstruction). Conclusions: SAR was found to be a promising alternative to FBP. The visibility of single spiculations was determined. The required diameter depends on both tissue composition and reconstruction

Volumetric breast density measurement for personalized screening : Accuracy, reproducibility, consistency, and agreement with visual assessment

Assessment of breast density at the point of mammographic examination could lead to optimized breast cancer screening pathways. The onsite breast density information may offer guidance of when to recommend supplemental imaging for women in a screening program. A software application (Insight BD, Siemens Healthcare GmbH) for fast onsite quantification of volumetric breast density is evaluated. The accuracy of the method is assessed using breast tissue equivalent phantom experiments resulting in a mean absolute error of 3.84%. Reproducibility of measurement results is analyzed using 8427 exams in total, comparing for each exam (if available) the densities determined from left and right views, from cranio-caudal and medio-lateral oblique views, from full-field digital mammograms (FFDM) and digital breast tomosynthesis (DBT) data and from two subsequent exams of the same breast. Pearson correlation coefficients of 0.937, 0.926, 0.950, and 0.995 are obtained. Consistency of the results is demonstrated by evaluating the dependency of the breast density on women's age. Furthermore, the agreement between breast density categories computed by the software with those determined visually by 32 radiologists is shown by an overall percentage agreement of 69.5% for FFDM and by 64.6% for DBT data. These results demonstrate that the software delivers accurate, reproducible, and consistent measurements that agree well with the visual assessment of breast density by radiologists