Breast Tomosynthesis: Aspects on detection and perception of simulated lesions

The aim of this thesis was to investigate aspects on detectability of simulated lesions (microcalcifications and masses) in digital mammography (DM) and breast tomosynthesis (BT). Perception in BT image volumes were also investigated by evaluating certain reading conditions. The first study concerned the effect of system noise on the detection of masses and microcalcification clusters in DM images using a free-response task. System noise has an impact on image quality and is related to the dose level. It was found to have a substantial impact on the detection of microcalcification clusters, whereas masses were relatively unaffected. The effect of superimposed tissue in DM is the major limitation hampering the detection of masses. BT is a three-dimensional technique that reduces the effect of superimposed tissue. In the following two studies visibility was quantified for both imaging modalities in terms of the required contrast at a fixed detection performance (92% correct decisions). Contrast detail plots for lesions with sizes 0.2, 1, 3, 8 and 25 mm were generated. The first study involved only an in-plane BT slice, where the lesion centre appeared. The second study repeated the same procedure in BT image volumes for 3D distributed microcalcification clusters and 8 mm masses at two dose levels. Both studies showed that BT needs substantially less contrast than DM for lesions above 1 mm. Furthermore, the contrast threshold increased as the lesion size increased for both modalities. This is in accordance with the reduced effect of superimposed tissue in BT. For 0.2 mm lesions, substantially more contrast was needed. At equal dose, DM was better than BT for 0.2 mm lesions and microcalcification clusters. Doubling the dose substantially improved the detection in BT. Thus, system noise has a substantial impact on detection. The final study evaluated reading conditions for BT image volumes. Four viewing procedures were assessed: free scroll browsing only or combined with initial cine loops at frame rates of 9, 14 and 25 fps. They were viewed on a wide screen monitor placed in vertical or horizontal positions. A free-response task and eye tracking were utilized to record the detection performance, analysis time, visual attention and search strategies. Improved reading conditions were found for horizontally aligned BT image volumes when using free scroll browsing only or combined with a cine loop at the fastest frame rate

Digital Breast Tomosynthesis : - the future screening tool for breast cancer?

Bakgrunn: Brystkreft er den vanligste kreftformen blant kvinner og en av de hyppigste årsakene til kreftdødsfall i Norge og globalt. Målsettingen med mammografiscreening er å oppdage brystkreft i et tidlig stadium og redusere dødeligheten av sykdommen. Studier har vist høyere deteksjon av screeningoppdagede krefttilfeller med digital brysttomosyntese som inkluderer ~200-250 bilder sammenlignet med standard digital mammografi (DM) med fire bilder. Vi utførte en randomisert kontrollert studie (RCT), Tomosyntese-studien i Bergen (To-Be1). Målsettingen med studien var å sammenligne tidligindikatorer i screening ved bruk av digital brysttomosyntese i kombinasjon med syntetiske 2D-bilder (DBT) versus standard DM. Avhandlingen inkluderer tre studier med følgende mål: Studie 1: Å sammenligne lesetid, stråledose, konsensus og tilbakekalling ved bruk av DBT og DM etter det første året av To-Be1. Studie 2: Å sammenligne tilbakekalling, falske positive screeningsresultater og screeningoppdaget kreft for kvinner med ulik mammografisk tetthet målt automatisk (Volpara tetthetsgrad, VDG 1-4) og med ulike screeningteknikker (DBT versus DM). Studie 3: Å undersøke fordeling av mammografiske funn hos kvinner tilbakekalt etter screening med DBT versus DM og analysere sammenhenger mellom mammografiske funn og det endelige resultatet av screeningundersøkelsen. Metode: Alle kvinner som deltok i screening utført i Bergen i løpet av 2016-2017 som en del av Mammografiprogrammet (n=32 976) ble invitert til å delta i To-Be1. Totalt aksepterte 89,3 % av kvinnene invitasjonen og ble randomisert til DBT eller DM. Etter uavhengig dobbelttyding med konsensus ble resultater etter DBT sammenlignet med DM. Mammografisk tetthet ble oppgitt som VDG 1-4, som er analog til kategoriene i BI-RADS´ 5. utgave. Radiologene klassifiserte mammografiske funn hos etterinnkalte kvinner etter en modifisert BI-RADS skala. Vi brukte deskriptive analyser og t-test for å sammenligne gjennomsnittsverdier, samt kji-kvadrat-test med tilhørende 95% konfidensintervall (KI) for å sammenligne kategorier. Log-binominale regresjonsmodeller ble brukt for å estimere relativ risiko. En p-verdi lavere enn 0,05 ble definert som statistisk signifikant. Vi brukte statistikkprogrammet STATA. Resultater: Studie 1: Gjennomsnittlig lesetid var 1:11 min:sek for DBT og 0:41 min:sek for DM i det første året av To-Be1. Det var ingen statistiske forskjeller i gjennomsnittlig stråledose for noen av tetthetskategoriene for DBT (2,96 mGy) versus DM (2,95 mGy). Tilbakekallingen var 3,0 % for DBT og 3,6 % for DM etter det første året med To-Be1. Studie 2: Etterundersøkelsesraten for kvinner med VDG 1 var 2,1% for DBT og 3,3% for DM, mens den var 3,2% for DBT og 4,3% for DM for de med VDG 2. Raten av falske positive screening resultater var 1,6% for DBT og 2,8% for DM for kvinner med VDG 1. For kvinner med VDG 2 var den 2,4% for DBT og 3,6 for DM. Ingen statistiske forskjeller i screeningoppdaget kreft ble funnet mellom DBT og DM for noen av tetthetskategoriene. Justert relativ risiko for tilbakekalling, falskt positivt screeningsresultat og screeningoppdaget kreft økte med VDG i DBT, mens det ikke ble funnet forskjeller i DM. Studie 3: Studien inkluderte 182 screeningdetekterte krefttilfeller (n=95 for DBT og n=87 for DM). Blant disse var 36,8% spikulerte masser for DBT mens det var 18,4% for DM. Kalk var det hyppigste mammografiske funnet for brystkrefttilfeller for de som var screenet med DM (23%). For DBT var andelen på 13,7%. Asymmetri, uskarp og skjult masse var mindre hyppig hos kvinner med et falsk positiv screening resultat etter screening med DBT versus DM. Konklusjon: Resultater fra To-Be1 indikerte at DBT var minst like god som DM når det gjelder etterundersøkelser og deteksjon av brystkreft, som betyr at DBT er trygt å bruke i screening. DBT var bedre egnet enn DM for kvinner med VDG 1 og 2 med hensyn til etterundersøkelsesrate og falske positive, mens deteksjon av brystkreft ikke var forskjellig. Det tok lengre tid å lese DBT enn DM bilder, og konsensus tok lengre tid med DBT. Mer kunnskap om forskjeller i mammografiske funn og sammenheng med screeningsresultater for DBT versus DM kan bidra til å ytterligere forbedre fordelene med DBT som et screeningverktøy.Background: Breast cancer is the most common cancer and one of the leading causes of cancer deaths in Norway and globally. Mammographic screening aims for early detection of breast cancer and reduced mortality from the disease. Studies have shown higher rates of screen-detected cancers for digital breast tomosynthesis including ~200-250 images compared to standard digital mammography (DM) including four images. We performed a randomized controlled trial (RCT), the Tomosynthesis trial in Bergen (To-Be1), were the aim was to compare early performance measures for digital breast tomosynthesis including synthesised 2D images (DBT) versus DM in screening. This thesis includes three studies with the following aims: Study 1: To compare preliminary results of reading time, radiation dose, consensus and recall for DBT and DM after the first year of To-Be1. Study 2: To compare recall, false positive screening results and screen-detected cancers by automated mammographic density (Volpara density grade, VDG 1-4) and screening technique (DBT versus DM). Study 3: To investigate distribution of mammographic features in women recalled after screening with DBT versus DM and assess associations between mammographic features and final outcome of the screening examination. Method: All women who attended the screening unit in Bergen during 2016-2017 as part of BreastScreen Norway (n=32 976) were invited to participate in To-Be1. In total, 89.3% of the women accepted the invitation and were randomized to undergo either DBT or DM. After independent double reading with consensus, results for DBT were compared with DM. Mammographic density were described by VDG 1-4 which are analogue to the categories in the BI-RADS 5th edition. The radiologists classified the mammographic features of recalled women according to a modified BI-RADS scale. We presented descriptive results and used t-tests to test for means, and chi-squared tests for categories with corresponding 95% confidence intervals (CI). Log-binominal regression models were used to estimate relative risks. A p-value lower than 0.05 was defined as statistically significant. We used STATA software. Results: Study 1: Mean reading time was 1:11 min:sec for DBT versus 0:41 min:sec for DM in the first year of To-Be1. Mean glandular dose did not differ statistically for women screened with DBT (2.96 mGy) versus DM (2.95 mGy). Recall was 3.0% for DBT and 3.6% for DM in the first year of To-Be1. Study 2: Recall rate for women with VDG 1 was 2.1% for DBT and 3.3% for DM, while it was 3.2% for DBT and 4.3% for DM for women with VDG 2. The rate of false positive screening results was 1.6% for DBT and 2.8% for DM for women with VDG 1. For women with VDG 2 it was 2.4% for DBT and 3.6% for DM. No statistical difference in screen-detected cancers was observed between DBT and DM in any density categories. Adjusted relative risk of recall, false positives and screen-detected cancers increased with VDG for DBT. No difference was found for DM. Study 3: The study included 182 screen detected cancers (n=95 DBT and n= 87 DM). 36.8% of those detected with DBT was spiculated mass, while it was 18.4 % for DM. Calcifications was the most frequent feature for breast cancer among those screened with DM (23.0%), which did not differ statistically from the 13.7% for DBT. Asymmetry, indistinct and obscured mass was less frequent in women with a false positive screening result after screening with DBT versus DM. Conclusion: Results from To-Be1 indicated DBT to be as least as good as DM in terms of recall and cancer detection, which means that DBT is safe for the women. DBT was superior to DM in women with VDG 1 and 2 (lower recall, fewer false positives, no difference in cancer detection). However, time spent on initial screen reading and on consensus was longer for DBT compared with DM. More knowledge of the differences in distribution of mammographic features and their association with screening outcome, might contribute to further improve the benefits of DBT as a screening tool for breast cancer.Doktorgradsavhandlin

Mammographic features and screening outcome in a randomized controlled trial comparing digital breast tomosynthesis and digital mammography

Purpose To compare the distribution of mammographic features among women recalled for further assessment after screening with digital breast tomosynthesis (DBT) versus digital mammography (DM), and to assess associations between features and final outcome of the screening, including immunohistochemical subtypes of the tumour. Methods This randomized controlled trial was performed in Bergen, Norway, and included 28,749 women, of which 1015 were recalled due to mammographic findings. Mammographic features were classified according to a modified BI-RADS-scale. The distribution were compared using 95 % confidence intervals (CI). Results Asymmetry was the most common feature of all recalls, 24.3 % (108/444) for DBT and 38.9 % (222/571) for DM. Spiculated mass was most common for breast cancer after screening with DBT (36.8 %, 35/95, 95 %CI: 27.2−47.4) while calcifications (23.0 %, 20/87, 95 %CI: 14.6−33.2) was the most frequent after DM. Among women screened with DBT, 0.13 % (95 %CI: 0.08−0.21) had benign outcome after recall due to indistinct mass while the percentage was 0.28 % (95 %CI: 0.20−0.38) for DM. The distributions were 0.70 % (95 %CI: 0.57−0.85) versus 1.46 % (95 %CI: 1.27−1.67) for asymmetry and 0.24 % (95 %CI: 0.16−0.33) versus 0.54 % (95 %CI: 0.43−0.68) for obscured mass, among women screened with DBT versus DM, respectively. Spiculated mass was the most common feature among women diagnosed with non-luminal A-like cancer after DBT and after DM. Conclusions Spiculated mass was the dominant feature for breast cancer among women screened with DBT while calcifications was the most frequent feature for DM. Further studies exploring the clinical relevance of mammographic features visible particularly on DBT are warranted.publishedVersio

Factors affecting recall rate and false positive fraction in breast cancer screening with breast tomosynthesis - A statistical approach.

In this study, we investigate which factors affect the false positive fraction (FPF) for digital breast tomosynthesis (DBT) compared to digital mammography (DM) in a screening population by using classification and regression trees (C&RT) and binary marginal generalized linear models. The data was obtained from the Malmö Breast Tomosynthesis Screening Trial, which aimed to compare the performance of DBT to DM in breast cancer screening. By using data from the first half of the study population (7500 women), a tree with the recall probability for different groups was calculated. The effect of age and breast density on the FPF was estimated using a binary marginal generalized linear model. Our results show that breast density and breast cancer were the main factors influencing recall. The FPF is mainly affected by breast density and increases with breast density for DBT and DM. In conclusion, the results obtained with C&RT are easy to interpret and similar to those obtained using binary marginal generalized linear models. The FPF is approximately 40% higher for DBT compared to DM for all breast density categories