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1.
  • Fieselmann, Andreas, et al. (author)
  • Volumetric breast density measurement for personalized screening : Accuracy, reproducibility, and agreement with visual assessment
  • 2018
  • In: 14th International Workshop on Breast Imaging (IWBI 2018). - : SPIE. - 9781510620070 ; 10718
  • Conference paper (peer-reviewed)abstract
    • 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 when to recommend supplemental imaging for women in a screening program. In this work, performance evaluation of a new software (Insight BD, Siemens Healthcare GmbH) for fast onsite quantification of volumetric breast density is presented. Accuracy of volumetric measurement is evaluated using breast tissue equivalent phantom experiments. Reproducibility of measurement results is analyzed using 8150 4-view mammography exams. Furthermore, agreement between breast density categories computed by the software with those determined visually by radiologists is examined. The results of the performance evaluation demonstrate that the software delivers accurate and reproducible measurements that agree well with the visual assessment of breast density by radiologists.
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2.
  • Fieselmann, Andreas, et al. (author)
  • Volumetric breast density measurement for personalized screening : Accuracy, reproducibility, consistency, and agreement with visual assessment
  • 2019
  • In: Journal of Medical Imaging. - 2329-4302. ; 6:3
  • Journal article (peer-reviewed)abstract
    • 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.
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3.
  • Förnvik, Daniel, et al. (author)
  • Comparison between software volumetric breast density estimates in breast tomosynthesis and digital mammography images in a large public screening cohort
  • 2019
  • In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 29:1, s. 330-336
  • Journal article (peer-reviewed)abstract
    • 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.
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4.
  • Förnvik, Hannie, et al. (author)
  • Towards determination of individual glandular dose
  • 2018
  • In: Medical Imaging 2018 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 9781510616356 ; 10573
  • Conference paper (peer-reviewed)abstract
    • 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.
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5.
  • Sartor, Hanna, et al. (author)
  • Changes in breast density over serial mammograms : A case-control study
  • 2020
  • In: European Journal of Radiology. - : Elsevier BV. - 0720-048X. ; 127
  • Journal article (peer-reviewed)abstract
    • 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.
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8.
  • Bakic, Predrag R., et al. (author)
  • Artifact reduction in simultaneous tomosynthesis and mechanical imaging of the breast
  • 2019
  • In: Medical Imaging 2019 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 9781510625433 ; 10948
  • Conference paper (peer-reviewed)abstract
    • Mechanical imaging (MI) uses a pressure sensor array to estimate the stiffness of lesions. Recent clinical studies have suggested that MI combined with digital mammography may reduce false positive findings and negative biopsies by over 30%. Digital breast tomosynthesis (DBT) has been adopted progressively in cancer screening. The tomographic nature of DBT improves lesion visibility by reducing tissue overlap in reconstructed images. For maximum benefit, DBT and MI data should be acquired simultaneously; however, that arrangement produces visible artifacts in DBT images due to the presence of the MI sensor array. We propose a method for reducing artifacts during the DBT image reconstruction. We modified the parameters of a commercial DBT reconstruction engine and investigated the conspicuity of artifacts in the resultant images produced with different sensor orientations. The method was evaluated using a physical anthropomorphic phantom imaged on top of the sensor. Visual assessment showed a reduction of artifacts. In a quantitative test, we calculated the artifact spread function (ASF), and compared the ratio of the mean ASF values between the proposed and conventional reconstruction (termed ASF ratio, RASF). We obtained a mean RASF of 2.74, averaged between two analyzed sensor orientations (45° and 90°). The performance varied with the orientation and the type of sensor structures causing the artifacts. RASF for wide connection lines was larger at 45° than at 90° (5.15 vs. 1.00, respectively), while for metallic contacts RASF was larger at 90° than at 45° (3.31 vs. 2.21, respectively). Future work will include a detailed quantitative assessment, and further method optimization in virtual clinical trials.
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9.
  • Dahlblom, Victor, et al. (author)
  • Malmö Breast ImaginG database: objectives and development
  • 2023
  • In: Journal of Medical Imaging. - 2329-4302. ; 10:6
  • Journal article (peer-reviewed)abstract
    • PurposeWe describe the design and implementation of the Malmö Breast ImaginG (M-BIG) database, which will support research projects investigating various aspects of current and future breast cancer screening programs. Specifically, M-BIG will provide clinical data to: 1. investigate the effect of breast cancer screening on breast cancer prognosis and mortality; 2. develop and validate the use of artificial intelligence and machine learning in breast image interpretation; and 3. develop and validate image-based radiological breast cancer risk profiles.ApproachThe M-BIG database is intended to include a wide range of digital mammography (DM) and digital breast tomosynthesis (DBT) examinations performed on women at the Mammography Clinic in Malmö, Sweden, from the introduction of DM in 2004 through 2020. Subjects may be included multiple times and for diverse reasons. The image data are linked to extensive clinical, diagnostic, and demographic data from several registries.ResultsTo date, the database contains a total of 451,054 examinations from 104,791 women. During the inclusion period, 95,258 unique women were screened. A total of 19,968 examinations were performed using DBT, whereas the rest used DM.ConclusionsWe describe the design and implementation of the M-BIG database as a representative and accessible medical image database linked to various types of medical data. Work is ongoing to add features and curate the existing data.
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10.
  • Dalene Skarping, Ida, et al. (author)
  • Neoadjuvant breast cancer treatment response; tumor size evaluation through different conventional imaging modalities in the NeoDense study
  • 2020
  • In: Acta Oncologica. - 1651-226X. ; 59:12, s. 1528-1537
  • Journal article (peer-reviewed)abstract
    • Neoadjuvant chemotherapy (NACT) is offered to an increasing number of breast cancer (BC) patients, and comprehensive monitoring of treatment response is of utmost importance. Several imaging modalities are available to follow tumor response, although likely to provide different clinical information. We aimed to examine the association between early radiological response by three conventional imaging modalities and pathological complete response (pCR). Further, we investigated the agreement between these modalities pre-, during, and post-NACT, and the accuracy of predicting pathological residual tumor burden by these imaging modalities post-NACT.
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11.
  • Dustler, Magnus, et al. (author)
  • A Study of the Feasibility of using slabbing to reduce Tomosynthesis Review Time
  • 2013
  • In: Medical Imaging 2013: Image Perception, Observer Performance, And Technology Assessment. - : SPIE. - 0277-786X .- 1996-756X. ; 8673, s. 86731-86731
  • Conference paper (peer-reviewed)abstract
    • This study aimed to investigate whether decreasing the amount of slices in breast tomosynthesis (BT) image volumes reduce reading time. BT slices were combined into so-called slabs, by reconstructing thin slices and merging them into thicker slabs. Sets of slabs where created from 35 clinical BT volumes with malignant or benignant findings and from 50 BT volumes drawn from screening sets (without any prior review). The image sets were reviewed in two separate sessions while the review time was recorded. A total of five experienced radiologists were employed for the image review. Additionally a VGA study was performed to compare slabbed images with the originals in order to ensure that the image quality was not significantly degraded. One set of 27 pathological cases (13 masses and 14 microcalcification clusters) and one of 22 subtle lesions that had been missed on digital mammography but detected on BT were presented to an experienced radiologist and 2 medical physicists who rated the quality of the slabbed versions relative to the originals. The study could find no significant degradation in image quality when using 2 mm slabs instead of 1 mm slices. There was no significant decrease in reading time on clinical cases (P=.133), but on screening images there was a significant decrease of 7.7 +/- 9.6 s from an average level of 32.2 +/- 14.5 s (P<.0001). This suggests that increasing slab thickness can reduce the time radiologists spend studying normal images by 20%.
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12.
  • Dustler, Magnus, et al. (author)
  • Breast compression in mammography: pressure distribution patterns
  • 2012
  • In: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 53:9, s. 973-980
  • Journal article (peer-reviewed)abstract
    • Background: Breast compression is important in mammography in order to improve image quality, better separate tissue components, and reduce absorbed dose to the breast. In this study we use a method to measure and visualize the distribution of pressure over a compressed breast in mammography. Purpose: To measure and describe the pressure distribution over the breast as a result of applied breast compression in mammography. Material and Methods: One hundred and three women aged 40.7-74.3 years (median, 48.9 years) invited for mammographic screening consented to take part in this study. They were subjected to two additional breast compressions of the left breast (standard force and approximately 50% reduction). Pressure images of the compressed breast were obtained using force sensing resistor (FSR) sensors placed underneath the compression plate. Subjects rated their experience of pain on a visual analogue scale (VAS). Results: Four pressure patterns were identified, fitting 81 of the 103 breasts, which were grouped accordingly. The remaining 22 breasts were found to correspond to a combination of any two patterns. Two groups (43 breasts) showed pressure mainly over the juxtathoracic part of the breast, had significantly greater breast thickness (P = 0.003) and had a lower mean pressure over dense tissue (P < 0.0001) than those with more evenly distributed pressure. Reducing compression force increased average breast thickness by 1.8 mm (P < 0.0001). Conclusion: The distribution of pressure differed greatly between breasts. In a large proportion of breasts the compression plate did not provide optimal compression of the breast, the compression force being absorbed in juxtathoracic structures.
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13.
  • Dustler, Magnus, et al. (author)
  • Can mechanical imaging increase the specificity of mammography screening?
  • 2017
  • In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 27:8, s. 3217-3225
  • Journal article (peer-reviewed)abstract
    • Objectives: This study aimed to investigate the effects of adding adjunct mechanical imaging to mammography breast screening. We hypothesized that mechanical imaging could detect increased local pressure caused by both malignant and benign breast lesions and that a pressure threshold for malignancy could be established. The impact of this on breast screening was investigated with regard to reductions in recall and biopsy rates. Methods: 155 women recalled from breast screening were included in the study, which was approved by the regional ethical review board (dnr 2013/620). Mechanical imaging readings were acquired of the symptomatic breast. The relative mean pressure on the suspicious area (RMPA) was defined and a threshold for malignancy was established. Results: Biopsy-proven invasive cancers had a median RMPA of 3.0 (interquartile range (IQR) = 3.7), significantly different from biopsy-proven benign at 1.3 (IQR = 1.0) and non-biopsied cases at 1.0 (IQR = 1.3) (P < 0.001). The lowest RMPA for invasive cancer was 1.4, with 23 biopsy-proven benign and 33 non-biopsied cases being below this limit. Had these women not been recalled, recall rates would have been reduced by 36% and biopsy rates by 32%. Conclusions: If implemented in a screening situation, this may substantially lower the number of false positives. Key Points: • Mechanical imaging is used as an adjunct to mammography in breast screening.• A threshold pressure can be established for malignant breast cancer.• Recalls and biopsies can be substantially reduced.
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14.
  • Dustler, Magnus, et al. (author)
  • Distribution of pressure on the breast in mammography using flexible and rigid compression plates : implications on patient handling
  • 2021
  • In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 62:12, s. 1583-1591
  • Journal article (peer-reviewed)abstract
    • Background: Breast compression in mammography is important but is a source of discomfort and has been linked to screening non-attendance. Reducing compression has little effect on breast thickness, and likely little effect on image quality, due to force being absorbed in the stiff juxta thoracic area instead of in the central breast. Purpose: To investigate whether a flexible compression plate can redistribute force to the central breast and whether this affects perceived pain. Material and Methods: Twenty-eight women recalled from mammography screening were compressed with flexible and rigid plates while retaining force and positioning, 15 in the craniocaudal (CC) view and 13 in the mediolateral oblique (MLO) view. Pressure distribution was continuously measured using pressure sensors. Results: The flexible plate showed greater mean breast pressure in both views: 2.8 versus 2.3 kPa for CC (confidence interval [CI] = 0.2–0.8) and 1.0 versus 0.5 kPa for MLO (CI = 0.2–0.6). The percentage of applied force distributed to the breast was significantly higher with the flexible plate, both on CC (36% vs. 22%, CI = 1–11) and MLO (30% vs. 14%, CI = 4–13). Conclusion: The flexible plate redistributes pressure to the central breast, achieving a better compression, particularly in the MLO view, though much applied force is still applied to the juxta thoracic region.
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15.
  • Dustler, Magnus, et al. (author)
  • The characteristics of malignant breast tumors imaged using a prototype mechanical imaging system as an adjunct to mammography
  • 2016
  • In: Breast Imaging : 13th International Workshop, IWDM 2016, Malmö, Sweden, June 19-22, 2016, Proceedings - 13th International Workshop, IWDM 2016, Malmö, Sweden, June 19-22, 2016, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783319415451 - 9783319415468 ; 9699, s. 282-288
  • Conference paper (peer-reviewed)abstract
    • Breast cancer is diagnosed by a combination of modalities. Measuring the elasto-mechanical properties of suspicious lesions, by e.g. ultrasound elastography, can help differentiate malignant from benign findings. Using a prototype Mechanical Imaging (MI) system as an adjunct to mammography, the aim of this study was to characterize tumors using MI and compare the readings to those from the contralateral breast. Thirteen bilateral MI sets from women with malignant breast lesions were included in this study, drawn from a larger set of 155 women recalled from screening. The results showed that mean lesion pressure was significantly greater than the mean pressure of the corresponding breast, 7.5 ± 7.0 kPa compared to 2.5 ± 1.6 kPa (P = 0.01). There was no evidence for a difference in mean pressure or standard deviation of the MI image between symptomatic and contralateral asymptomatic breasts (P = 0.24 and 0.68). The results support that it is possible to use MI to distinguish malignant cancers from normal breast tissue. Still, further investigations of the characteristics of benign lesions are necessary to ascertain the usefulness of the system.
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16.
  • Dustler, Magnus, et al. (author)
  • The Effect of Breast Positioning on Breast Compression in Mammography: a Pressure Distribution Perspective
  • 2012
  • In: Medical Imaging 2012: Physics of Medical Imaging. - : SPIE. - 1996-756X .- 0277-786X. ; 8313
  • Conference paper (peer-reviewed)abstract
    • 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.
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17.
  • Eriksson, Mikael, et al. (author)
  • Identification of Women at High Risk of Breast Cancer Who Need Supplemental Screening
  • 2020
  • In: Radiology. - : Radiological Society of North America (RSNA). - 1527-1315 .- 0033-8419. ; 297:2, s. 327-333
  • Journal article (peer-reviewed)abstract
    • Background Mammography screening reduces breast cancer mortality, but a proportion of breast cancers are missed and are detected at later stages or develop during between-screening intervals. Purpose To develop a risk model based on negative mammograms that identifies women likely to be diagnosed with breast cancer before or at the next screening examination. Materials and Methods This study was based on the prospective screening cohort Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA), 2011-2017. An image-based risk model was developed by using the Stratus method and computer-aided detection mammographic features (density, masses, microcalcifications), differences in the left and right breasts, and age. The lifestyle extended model included menopausal status, family history of breast cancer, body mass index, hormone replacement therapy, and use of tobacco and alcohol. The genetic extended model included a polygenic risk score with 313 single nucleotide polymorphisms. Age-adjusted relative risks and tumor subtype specific risks were estimated by using logistic regression, and absolute risks were calculated. Results Of 70 877 participants in the KARMA cohort, 974 incident cancers were sampled from 9376 healthy women (mean age, 54 years ± 10 [standard deviation]). The area under the receiver operating characteristic curve (AUC) for the image-based model was 0.73 (95% confidence interval [CI]: 0.71, 0.74). The AUCs for the lifestyle and genetic extended models were 0.74 (95% CI: 0.72, 0.75) and 0.77 (95% CI: 0.75, 0.79), respectively. There was a relative eightfold difference in risk between women at high risk and those at general risk. High-risk women were more likely to be diagnosed with stage II cancers and with tumors 20 mm or larger and were less likely to have stage I and estrogen receptor-positive tumors. The image-based model was validated in three external cohorts. Conclusion By combining three mammographic features, differences in the left and right breasts, and optionally lifestyle factors and family history and a polygenic risk score, the model identified women at high likelihood of being diagnosed with breast cancer within 2 years of a negative screening examination and in possible need of supplemental screening.
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  • Förnvik, Daniel, et al. (author)
  • A human observer study for evaluation and optimization of reconstruction methods in breast tomosynthesis using clinical cases
  • 2011
  • In: Medical Imaging 2011: Physics of Medical Imaging. - : SPIE. - 0277-786X .- 1996-756X. ; 7961, s. 79615-79615
  • Conference paper (peer-reviewed)abstract
    • In breast tomosynthesis1 (BT) a number of 2D projection images are acquired from different angles along a limited arc. The imaged breast volume is reconstructed from the projection images, providing 3D information. The purpose of the study was to investigate and optimize different reconstruction methods for BT in terms of image quality using human observers viewing clinical cases. Sixty-six cases with suspected masses and calcifications were collected from 55 patients. Four different reconstructions of each image set were evaluated by four observers (two experienced radiologists, two experienced medical physicists): filtered back projection (FBP), iterative adapted FBP (iFBP) and two ML-convex iterative algorithm (MLCI) reconstructions (8 and 10 iterations) that differed in noise level and contrast of clinical details. Representation of masses and microcalcifications was evaluated. The structures were rated according to the overall appearance in a rank-order study. The differently reconstructed images of the same structure were displayed side by side in random order. The observers were forced to rank the order of the different reconstructed images and their proportions at each rank were scored. The results suggest that even though the FBP contains most noise its reconstructions are considered best overall, followed by iFBP, which contains least noise. In both FBP and iFBP methods the sharp borders and mass speculations were better represented than in iterative reconstructions while out-of-plane artifacts were better suppressed in the latter. However, in clinical practice the differences between the reconstructions may be considered negligible.
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19.
  • Förnvik, Daniel, et al. (author)
  • Breast tomosynthesis: Accuracy of tumor measurement compared with digital mammography and ultrasonography.
  • 2010
  • In: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 51, s. 240-247
  • Journal article (peer-reviewed)abstract
    • Background: Mammographic tumor size measurement can be difficult because breast structures are superimposed onto a two-dimensional (2D) plane, potentially obscuring the tumor outline. Breast tomosynthesis (BT) is a 3D X-ray imaging technique in which low-dose images are acquired over a limited angular range at a total dose comparable to digital mammography (DM). These low-dose images are used to mathematically reconstruct a 3D image volume of the breast, thus reducing the problem of superimposed tissue. Purpose: To investigate whether breast cancer size can be more accurately assessed with breast tomosynthesis than with digital mammography and ultrasonography (US), by reducing the disturbance effect of the projected anatomy. Material and Methods: A prototype BT system was used. The main inclusion criterion for BT examination was subtle but suspicious findings of breast cancer on 2D mammography. Sixty-two women with 73 breast cancers were included. BT, DM, and US sizes were measured independently by experienced radiologists without knowledge of the pathology results, which were used as reference. Results: The tumor outline could be determined in significantly more cases with BT (63) and US (60) than DM (49). BT and US size correlated well with pathology (R=0.86 and R=0.85, respectively), and significantly better than DM size (R=0.71). Accordingly, staging was significantly more accurate with BT than with DM. Conclusion: The study indicates that BT is superior to DM in the assessment of breast tumor size and stage.
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20.
  • Förnvik, Daniel, et al. (author)
  • Detection of circulating tumor cells and circulating tumor DNA before and after mammographic breast compression in a cohort of breast cancer patients scheduled for neoadjuvant treatment
  • 2019
  • In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 177:2, s. 447-455
  • Journal article (peer-reviewed)abstract
    • PurposeIt is not known if mammographic breast compression of a primary tumor causes shedding of tumor cells into the circulatory system. Little is known about how the detection of circulating biomarkers such as circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) is affected by breast compression intervention.MethodsCTCs and ctDNA were analyzed in blood samples collected before and after breast compression in 31 patients with primary breast cancer scheduled for neoadjuvant therapy. All patients had a central venous access to allow administration of intravenous neoadjuvant chemotherapy, which enabled blood collection from superior vena cava, draining the breasts, in addition to sampling from a peripheral vein.ResultsCTC and ctDNA positivity was seen in 26% and 65% of the patients, respectively. There was a significant increase of ctDNA after breast compression in central blood (p = 0.01), not observed in peripheral testing. No increase related with breast compression was observed for CTC. ctDNA positivity was associated with older age (p = 0.05), and ctDNA increase after breast compression was associated with high Ki67 proliferating tumors (p = 0.04). CTCs were more abundant in central compared to peripheral blood samples (p = 0.04).ConclusionsThere was no significant release of CTCs after mammographic breast compression but more CTCs were present in central compared to peripheral blood. No significant difference between central and peripheral levels of ctDNA was observed. The small average increase in ctDNA after breast compression is unlikely to be clinically relevant. The results give support for mammography as a safe procedure from the point of view of CTC and ctDNA shedding to the blood circulation. The results may have implications for the standardization of sampling procedures for circulating tumor markers.
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21.
  • Förnvik, Daniel, et al. (author)
  • ESTIMATES OF BREAST CANCER GROWTH RATE FROM MAMMOGRAMS AND ITS RELATION TO TUMOUR CHARACTERISTICS.
  • 2016
  • In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 169, s. 151-157
  • Journal article (peer-reviewed)abstract
    • This study aimed to investigate the growth rate of 31 consecutive invasive breast cancers based on volume measures on at least two serial mammograms and its relation to histopathological findings. The average tumour volume-doubling time in all invasive breast cancer subtypes was 282 d (range 46-749 d). Grade III breast cancers had a significantly shorter average tumour volume-doubling time of 105 d (range 46-157 d) compared with Grade I and II tumours (average of 296 d, range 147-531 d and average of 353 d, range 139-749 d, respectively) (p = 0.002). Multiple linear regression identified that tumour volume-doubling time was positively associated with patient age, histological grade and progesterone receptor expression and inversely associated with axillary lymph node involvement, human epidermal growth factor receptor 2 and Ki-67 expression (p < 0.001). In conclusion, tumour volume-doubling time as estimated on serial mammography may provide important prognostic information relevant for clinical decision-making.
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22.
  • Förnvik, Daniel (author)
  • Measurement of Tumor Extent and Effects of Breast Compression in Digital Mammography and Breast Tomosynthesis
  • 2013
  • Doctoral thesis (other academic/artistic)abstract
    • 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.
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23.
  • Förnvik, Daniel, et al. (author)
  • No evidence for shedding of circulating tumor cells to the peripheral venous blood as a result of mammographic breast compression.
  • 2013
  • In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 141:2, s. 187-195
  • Journal article (peer-reviewed)abstract
    • This pilot study aimed to investigate whether mammographic compression procedures might cause shedding of tumor cells into the circulatory system as reflected by circulating tumor cell (CTC) count in peripheral venous blood samples. From March to October 2012, 24 subjects with strong suspicion of breast malignancy were included in the study. Peripheral blood samples were acquired before and after mammography. Enumeration of CTCs in the blood samples was performed using the CellSearch(®) system. The pressure distribution over the tumor-containing breast was measured using thin pressure sensors. The median age was 66.5 years (range, 51-87 years). In 22 of the 24 subjects, breast cancer was subsequently confirmed. The difference between the average mean tumor pressure 6.8 ± 5.3 kPa (range, 1.0-22.5 kPa) and the average mean breast pressure 3.4 ± 1.6 kPa (range, 1.5-7.1 kPa) was statistically significant (p < 0.001), confirming that there was increased pressure over the tumor. The median pathological tumor size was 19 mm (range, 9-30 mm). Four subjects (17 %) were CTC positive before compression and two of these (8 %) were also CTC positive after compression. A total of seven CTCs were isolated with a mean size of 8 × 6 μm(2) (range of the longest diameter, 5-12 μm). The study supports the view that mammography is a safe procedure from the point of view of tumor cell shedding to the peripheral blood.
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24.
  • Förnvik, Daniel, et al. (author)
  • Pressure distribution in mammography: compression of breasts with malignant tumor masses
  • 2013
  • In: Medical Imaging 2013: Physics of Medical Imaging. - : SPIE. - 1996-756X .- 0277-786X. ; 8668, s. 86684-86684
  • Conference paper (peer-reviewed)abstract
    • The pressure distribution over a compressed breast is in general heterogeneous. In this study we investigated the pressure distribution over compressed breasts with tumor masses. Twenty-two women either recalled for work-up of findings suspicious for breast cancer in the screening program or with clinically suspected findings were included in the study. Twenty-one lesions turned out to be malignant and one benign. The distribution of compression pressure was measured using thin FSR (Force Sensing Resistor) pressure sensors attached to the compression plate. The pressure over the breast was ascertained by acquiring an x-ray image of the compressed breast with the pressure sensors present. The pressure data and the mammogram were used to create a composite image with pressure data displayed as a color overlay. The malignant tumor area generally matched an elevated pressure area and this pressure was generally higher than the pressure over surrounding parenchyma. In 11 out of 22 (50%) subjects the maximum pressure over the breast was located over the tumor. Only 4 out of 22 (18%) masses had a lower tumor mean pressure compared to the mean pressure over the breast (including one small < 10 mm tumor and one benign structure). The results suggest that tumors are stiffer, thus, absorbing more pressure compared to the surrounding parenchyma and that this property can be quantified. Refined pressure techniques could possibly be used to demonstrate the relative elasticity distribution in breast tissue, which might provide valuable differential diagnostic information.
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25.
  • Förnvik, Daniel, et al. (author)
  • THE EFFECT OF REDUCED BREAST COMPRESSION IN BREAST TOMOSYNTHESIS: HUMAN OBSERVER STUDY USING CLINICAL CASES.
  • 2010
  • In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; Apr 7, s. 118-123
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate whether the compression force used with conventional mammography can be reduced with breast tomosynthesis (BT), without adversely affecting the visualisation of normal and pathological structures. Forty-five women were examined with BT using full (same as for 2D mammography) and half compression force. Both examinations were performed with the same acquisition parameters. A total of 103 paired structure images were evaluated according to specified image quality criteria. Three experienced radiologists participated in the study. They had to make a forced choice, i.e. choose the image they felt best fulfilled the image quality criteria. The results showed no evident difference in the image quality, indicating that BT may be performed with substantially less compression force compared with 2D mammography. A majority of the examined women felt that half compression was more comfortable than full compression.
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26.
  • Förnvik, Daniel, et al. (author)
  • The role of breast tomosynthesis in a predominantly dense breast population at a tertiary breast centre : breast density assessment and diagnostic performance in comparison with MRI
  • 2018
  • In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 28:8, s. 3194-3203
  • Journal article (peer-reviewed)abstract
    • Objectives: To compare breast density measured on digital breast tomosynthesis (DBT) (BI-RADS-based breast composition and fully-automatic estimation) and magnetic resonance imaging (MRI) (BI-RADS amount of fibroglandular tissue), and to evaluate the diagnostic performance in terms of sensitivity and specificity of DBT and MRI in a predominantly dense breast population. Methods: Between 2015 and 2016, 152 women with 103 breast malignancies, who underwent 3-T breast MRI and DBT within 2 months’ time, were enrolled in this study. Breast composition/fibroglandular tissue and findings on DBT (two readers) and MRI were reported using BI-RADS 5th edition. Digital mammography images were analysed for breast percent density (PD) using the Libra software tool. Results: A majority of women had dense breasts as categorised by breast composition c (heterogeneously dense) (68%) and d (extremely dense) (15%). The mean PD was 44% (range, 18-89%) and the correlation between breast composition and PD was r = 0.6. The diagnostic performance of MRI was significantly higher compared to DBT for one reader as described by the area under the receiver operating characteristic (ROC) curve (p = 0.004) and of borderline significance for the other reader (p = 0.052). Conclusions: MRI had higher diagnostic performance than DBT in a dense breast population in the tertiary setting. Key Points: • MRI had higher diagnostic performance than DBT in a dense breast population• Diagnostic performance of DBT was comparable to MRI in women with fatty breasts• MRI was superior to DBT in preoperative breast cancer size assessment
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27.
  • Loman, Niklas, et al. (author)
  • Abstract P2-02-09: Breast cancer subtype distribution and circulating tumor DNA in response to neoadjuvant chemotherapy: Experiences from a preoperative cohort within SCAN-B
  • 2018
  • In: Cancer research. Supplement. - 1538-7445. ; 78:4
  • Conference paper (peer-reviewed)abstract
    • Introduction: Preoperative chemotherapy in early breast cancer increases the rate of breast preservation and provides prognostic information. In the case of residual disease, a change in subtypes may be observed. Sensitive and reproducible biomarkers predicting treatment response early during the treatment course are needed in order to better exploit the potential benefit of an individualized preoperative treatment.Material and Methods: In an ongoing prospective study within the population-based SCAN-B project (NCT02306096), patients undergoing preoperative chemotherapy for early or locally recurrent breast cancer have been treated with iv Epirubicin and Cyclophosphamide q3w x 3 in sequence with either Docetaxel q3w x 3 or Paclitaxel q1w x 9 with a preoperative intent. HER2-positive cases also received HER2-directed treatment. At baseline, patients were staged using sentinel node biopsy for clinically node-negative patients and CT scan for cytologically confirmed node-positive cases. A clinical core needle biopsy as well as tissue from the surgical specimen was collected for determination of conventional biomarkers including ER, PgR, HER2 and Ki67. Tumor biopsies for biomolecule-extraction and RNA-sequencing were taken using ultrasound guidance and collected fresh in RNAlater at baseline, after 2 treatment cycles, as well as at surgery. Blood plasma samples were collected at baseline, after one-, three-, and six- 3w treatment cycles, and post-surgery. Using RNA-sequencing data, somatic mutations were identified in the tumor biopsies and personalized analyses for circulating tumor DNA (ctDNA) were performed. A pathological complete remission (pCR) was defined as the complete disappearance of invasive breast cancer in the breast and axilla at time of definitive surgery. Subtyping was performed using modified St Gallen criteria (2013).Results: Thus far, 45 patients aged 24-74 years have been included, of which 34 (76 %) were clinical stage 2 and 11 (24%) were stage 3. The subtype distribution at baseline was five Luminal A-like (11 %), 21 Luminal B-like (HER2 negative) (47 %), 8 HER2-positive (18 %) and 11 Triple-negative (ductal) (24 %). The rates of pCR in 38 operated cases to date were 0/3 Luminal A-like, 3/19 Luminal B-like (HER2 negative), 2/8 HER2-positive, and 4/7 Triple-negative (overall 24 % pCR rate). One patient did not undergo surgery due to clinically progressive disease. In 25 cases with evaluable residual disease at surgery, there was a shift in the subtype in 13 (52 %), the majority of which represented a transition from Luminal B to Luminal A. No Triple-negative cases underwent a change in subtype during treatment. Results of the ctDNA analyses will be presented at the meeting.Discussion: We have established an infrastructure allowing for an extensive evaluation of preoperative chemotherapy in early breast cancer. The goal is to develop methods to refine response-guided treatment in early breast cancer using molecular responses in the tumor as well as in the blood circulation. The patients continue to be prospectively monitored with iterative ctDNA analyses during follow-up.
  •  
28.
  • Lång, Kristina, et al. (author)
  • Can horizontally oriented breast tomosynthesis image volumes or the use of a systematic search strategy improve interpretation? An eye tracking and free response human observer study
  • 2011
  • In: Proc. SPIE. - : SPIE. ; 7966:796606
  • Conference paper (peer-reviewed)abstract
    • Our aim was to evaluate if there is a benefit in diagnostic accuracy and efficiency of viewing breast tomosynthesis (BT) image volumes presented horizontally oriented, but also to evaluate the use of a systematic search strategy where the breast is divided, and analyzed consecutively, into two sections. These image presentations were compared to regular vertical image presentation. All methods were investigated using viewing procedures consisting of free scroll volume browsing, and a combination of initial cine loops at three different frame rates (9, 14, 25 fps) terminated upon request followed by free scroll volume browsing if needed. Fifty-five normal BT image volumes in MLO view were collected. In these, simulated lesions (20 masses and 20 clusters of microcalcifications) were randomly inserted, creating four unique image sets for each procedure. Four readers interpreted the cases in a random order. Their task was to locate the lesions, mark and assign a five level confidence scale. The diagnostic accuracy was analyzed using Jackknife Free Receiver Operating Characteristics (JAFROC). Time efficiency and visual search behavior were also investigated using eye tracking. Results indicate there was no statistically significant difference in JAFROC FOM between the different image presentations, although visual search was more time efficient when viewing horizontally oriented image volumes in medium cine loops.
  •  
29.
  • Lång, Kristina, et al. (author)
  • Optimizing viewing procedures of breast tomosynthesis image volumes using eye tracking combined with a free response human observer study
  • 2011
  • In: Medical Imaging 2011: Image Perception, Observer Performance, and Technology Assessment / SPIE Proceedings. - : SPIE. ; 7966:796602
  • Conference paper (peer-reviewed)abstract
    • The purpose of this study was to evaluate four different viewing procedures as part of improving viewing conditions of breast tomosynthesis (BT) image volumes. The procedures consisted of free scroll volume browsing, and a combination of initial cine loops at three different frame rates (9, 14 and 25 fps) terminated upon request followed by free scroll volume browsing. Fifty-five normal BT image volumes in MLO view were collected. In these, simulated lesions (20 masses and 20 clusters of microcalcifications) were randomly inserted, creating four unique image sets for each procedure. Four readers interpreted the cases in a random order. Their task was to locate a lesion, mark and assign a five level confidence scale. The diagnostic accuracy was analyzed using Jackknife Free Receiver Operating Characteristics (JAFROC). Time efficiency and visual search behavior were also investigated using eye tracking. The results indicate that there was no statistically significant difference in JAFROC FOM between the different viewing procedures, however the medium cine loop speed seemed to be the preferred viewing procedure in terms of total analyze time and dwell time.
  •  
30.
  • Olinder, Jakob, et al. (author)
  • Impact of breast density on diagnostic accuracy in digital breast tomosynthesis versus digital mammography : results from a European screening trial
  • 2023
  • In: Breast Cancer Research. - 1465-5411. ; 25:1
  • Journal article (peer-reviewed)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.
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31.
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32.
  • Skarping, Ida, et al. (author)
  • Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients
  • 2021
  • In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 32:3, s. 251-260
  • Journal article (peer-reviewed)abstract
    • Purpose: Personalized cancer treatment requires predictive biomarkers, including image-based biomarkers. Breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) are in a clinically vulnerable situation with the tumor present. This study investigated whether mammographic density (MD), assessed pre-NACT, is predictive of pathological complete response (pCR). Methods: A total of 495 BC patients receiving NACT in Sweden 2005–2019 were included, merged from two different cohorts. Cohort 1 was retrospectively collected (n = 295) and cohort 2 was prospectively collected (n = 200). Mammograms were scored for MD pre-NACT according to the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. The association between MD and accomplishing pCR post-NACT was analyzed using logistic regression models—for the whole cohort, stratified by menopausal status, and in different St. Gallen surrogate subtypes. Results: In comparison to patients with low MD (BI-RADS a), the multivariable-adjusted odds ratio (OR) of accomplishing pCR following NACT was on a descending scale: 0.62 (95% confidence interval (CI) 0.24–1.57), 0.38 (95% CI 0.14–1.02), and 0.32 (95% CI 0.09–1.08) for BI-RADS b, c, and d, respectively. For premenopausal patients selectively, the corresponding point estimates were lower, although wider CIs: 0.31 (95% CI 0.06–1.62), 0.24 (95% CI 0.04–1.27), and 0.13 (95% CI 0.02–0.88). Subgroup analyses based on BC subtypes resulted in imprecise estimates, i.e., wide CIs. Conclusions: It seemed as though patients with higher MD at baseline were less likely to reach pCR after NACT—a finding more pronounced in premenopausal women. Larger multicenter studies are needed to enable analyses and interpretation for different BC subtypes.
  •  
33.
  • Skarping, Ida, et al. (author)
  • Mammographic density changes during neoadjuvant breast cancer treatment : NeoDense, a prospective study in Sweden
  • 2020
  • In: Breast. - : Elsevier BV. - 0960-9776. ; 53, s. 33-41
  • Journal article (peer-reviewed)abstract
    • Objectives: To assess if mammographic density (MD) changes during neoadjuvant breast cancer treatment and is predictive of a pathological complete response (pCR). Methods: We prospectively included 200 breast cancer patients assigned to neoadjuvant chemotherapy (NACT) in the NeoDense study (2014–2019). Raw data mammograms were used to assess MD with a fully automated volumetric method and radiologists categorized MD using the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. Logistic regression was used to calculate odds ratios (OR) for pCR comparing BI-RADS categories c vs. a, b, and d as well as with a 0.5% change in percent dense volume adjusting for baseline characteristics. Results: The overall median age was 53.1 years, and 48% of study participants were premenopausal pre-NACT. A total of 23% (N = 45) of the patients accomplished pCR following NACT. Patients with very dense breasts (BI-RADS d) were more likely to have a positive axillary lymph node status at diagnosis: 89% of the patients with very dense breasts compared to 72% in the entire cohort. A total of 74% of patients decreased their absolute dense volume during NACT. The likelihood of accomplishing pCR following NACT was independent of volumetric MD at diagnosis and change in volumetric MD during treatment. No trend was observed between decreasing density according to BI-RADS and the likelihood of accomplishing pCR following NACT. Conclusions: The majority of patients decreased their MD during NACT. We found no evidence of MD as a predictive marker of pCR in the neoadjuvant setting.
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34.
  • Skarping, Ida, et al. (author)
  • Mammographic density is a potential predictive marker of pathological response after neoadjuvant chemotherapy in breast cancer
  • 2019
  • In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1, s. 1272-1272
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Our aim is to study if mammographic density (MD) prior to neoadjuvant chemotherapy is a predictive factor in accomplishing a pathological complete response (pCR) in neoadjuvant-treated breast cancer patients.METHODS: Data on all neoadjuvant treated breast cancer patients in Southern Sweden (2005-2016) were retrospectively identified, with patient and tumor characteristics retrieved from their medical charts. Diagnostic mammograms were used to evaluate and score MD as categorized by breast composition with the Breast Imaging-Reporting and Data System (BI-RADS) 5th edition. Logistic regression was used in complete cases to assess the odds ratios (OR) for pCR compared to BI-RADS categories (a vs b-d), adjusting for patient and pre-treatment tumor characteristics.RESULTS: A total of 302 patients were included in the study population, of which 57 (18.9%) patients accomplished pCR following neoadjuvant chemotherapy. The number of patients in the BI-RADS category a, b, c, and d were separately 16, 120, 140, and 26, respectively. In comparison to patients with BI-RADS breast composition a, patients with denser breasts had a lower OR of accomplishing pCR: BI-RADS b 0.32 (95%CI 0.07-0.1.5), BI-RADS c 0.30 (95%CI 0.06-1.45), and BI-RADS d 0.06 (95%CI 0.01-0.56). These associations were measured with lower point estimates, but wider confidence interval, in premenopausal patients; OR of accomplishing pCR for BI-RADS d in comparison to BI-RADS a: 0.03 (95%CI 0.00-0.76).CONCLUSIONS: The likelihood of accomplishing pCR is indicated to be lower in breast cancer patients with higher MD, which need to be analysed in future studies for improved clinical decision-making regarding neoadjuvant treatment.
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35.
  • Skarping, Ida, et al. (author)
  • Predicting pathological axillary lymph node status with ultrasound following neoadjuvant therapy for breast cancer
  • 2021
  • In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 189:1, s. 131-144
  • Journal article (peer-reviewed)abstract
    • Purpose: High-performing imaging and predictive markers are warranted to minimize surgical overtreatment of the axilla in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Here we have investigated whether axillary ultrasound (AUS) could identify axillary lymph node (ALN) metastasis (ALNM) pre-NACT and post-NACT for BC. The association of tumor, AUS features and mammographic density (MD) with axillary-pathological complete response (axillary-pCR) post-NACT was also assessed. Methods: The NeoDense-study cohort (N = 202, NACT during 2014–2019), constituted a pre-NACT cohort, whereas patients whom had a cytology verified ALNM pre-NACT and an axillary dissection performed (N = 114) defined a post-NACT cohort. AUS characteristics were prospectively collected pre- and post-NACT. The diagnostic accuracy of AUS was evaluated and stratified by histological subtype and body mass index (BMI). Predictors of axillary-pCR were analyzed, including MD, using simple and multivariable logistic regression models. Results: AUS demonstrated superior performance for prediction of ALNM pre-NACT in comparison to post-NACT, as reflected by the positive predictive value (PPV) 0.94 (95% CI 0.89–0.97) and PPV 0.76 (95% CI 0.62–0.87), respectively. We found no difference in AUS performance according to neither BMI nor histological subtype. Independent predictors of axillary-pCR were: premenopausal status, ER-negativity, HER2-overexpression, and high MD. Conclusion: Baseline AUS could, to a large extent, identify ALNM; however, post-NACT, AUS was insufficient to determine remaining ALNM. Thus, our results support the surgical staging of the axilla post-NACT. Baseline tumor biomarkers and patient characteristics were predictive of axillary-pCR. Larger, multicenter studies are needed to evaluate the performance of AUS post-NACT.
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36.
  • Skarping, Ida, et al. (author)
  • The association between body mass index and pathological complete response in neoadjuvant-treated breast cancer patients
  • 2022
  • In: Acta Oncologica. - 0284-186X. ; 61:6, s. 731-737
  • Journal article (peer-reviewed)abstract
    • Background: Obesity seems to be associated with a poorer response to adjuvant chemotherapy in breast cancer (BC); however, associations in the neoadjuvant chemotherapy (NACT) setting and according to menopausal status are less studied. This study aims to investigate the association between pretreatment body mass index (BMI) and pathological complete response (pCR) following NACT in BC according to menopausal and estrogen receptor (ER) status. Material and Methods: The study cohort consisted of 491 patients receiving NACT in 2005–2019. Based on pre-NACT patient and tumor characteristics, the association between BMI and achieving pCR was analyzed using logistic regression models (crude and adjusted models (age, tumor size, and node status)) with stratification by menopausal and ER status. Results: In the overall cohort, being overweight (BMI ≥25) compared by being normal-weight (BMI <25), increased the odds of accomplishing pCR by 15%. However, based on the 95% confidence interval (CI) the data were compatible with associations within the range of a decrease of 30% to an increase of 89%. Stratification according to menopausal status also showed no strong association: the odds ratio (OR) of accomplishing pCR in overweight premenopausal patients compared with normal-weight premenopausal patients was 1.76 (95% CI 0.88–3.55), whereas for postmenopausal patients the corresponding OR was 0.71 (95% CI 0.35–1.46). Discussion: In a NACT BC cohort of 491 patients, we found no evidence of high BMI as a predictive factor of accomplishing pCR, neither in the whole cohort nor stratified by menopausal status. Given the limited precision in our results, larger studies are needed before considering BMI in clinical decision-making regarding NACT or not.
  •  
37.
  • Svahn, Tony, et al. (author)
  • THE DIAGNOSTIC ACCURACY OF DUAL-VIEW DIGITAL MAMMOGRAPHY, SINGLE-VIEW BREAST TOMOSYNTHESIS AND A DUAL-VIEW COMBINATION OF BREAST TOMOSYNTHESIS AND DIGITAL MAMMOGRAPHY IN A FREE-RESPONSE OBSERVER PERFORMANCE STUDY.
  • 2010
  • In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139, s. 113-117
  • Journal article (peer-reviewed)abstract
    • The purpose of the present study was to compare the diagnostic accuracy of dual-view digital mammography (DM), single-view breast tomosynthesis (BT) and BT combined with the contralateral DM view. Patients with subtle lesions were selected to undergo BT examinations. Two radiologists who are non-participants in the study and have experience in using DM and BT determined the locations and extents of lesions in the images. Five expert mammographers interpreted the cases using the free-response paradigm. The task was to mark and rate clinically reportable findings suspicious for malignancy and clinically relevant benign findings. The marks were scored with reference to the outlined regions into lesion localization or non-lesion localization, and analysed by the jackknife alternative free-response receiver operating characteristic method. The analysis yielded statistically significant differences between the combined modality and dual-view DM (p < 0.05). No differences were found between single-view BT and dual-view DM or between single-view BT and the combined modality.
  •  
38.
  • Timberg, Pontus, et al. (author)
  • Breast density assessment using breast tomosynthesis images
  • 2016
  • In: Breast Imaging : 13th International Workshop, IWDM 2016, Malmö, Sweden, June 19-22, 2016, Proceedings - 13th International Workshop, IWDM 2016, Malmö, Sweden, June 19-22, 2016, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783319415451 - 9783319415468 ; 9699, s. 197-202
  • Conference paper (peer-reviewed)abstract
    • In this work we evaluate an approach for breast density assessment of digital breast tomosynthesis (DBT) data using the central projection image. A total of 348 random cases (both FFDM CC and MLO views and DBT MLO views) were collected using a Siemens Mammomat Inspiration tomosynthesis unit at Unilabs, Malmö. The cases underwent both BI-RADS 5th Edition labeling by radiologists and automated volumetric breast density analysis (VBDA) by an algorithm. Preliminary results showed an observed agreement of 70% (weighted Kappa, κ = 0.73) between radiologists and VBDA using FFDM images and 63% (κ = 0.62) for radiologists and VBDA using DBT images. Comparison between densities for FFDM and DBT resulted in high correlation (r = 0.94) and an observed agreement of 72% (κ = 0.76). The automated analysis is a promising approach using low dose central projection DBT images in order to get radiologist- like density ratings similar to results obtained from FFDM.
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39.
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40.
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41.
  • Timberg, Pontus, et al. (author)
  • Investigation of viewing procedures for interpretation of breast tomosynthesis image volumes: a detection-task study with eye tracking.
  • 2013
  • In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 23:4, s. 997-1005
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To evaluate the efficiency of different methods of reading breast tomosynthesis (BT) image volumes. METHODS: All viewing procedures consisted of free scroll volume browsing and three were combined with initial cine loops at three different frame rates (9, 14 and 25 fps). The presentation modes consisted of vertically and horizontally orientated BT image volumes. Fifty-five normal BT image volumes in mediolateral oblique view were collected. In these, simulated lesions were inserted, creating four unique image sets, one for each viewing procedure. Four observers interpreted the cases in a free-response task. Time efficiency, visual attention and search were investigated using eye tracking. RESULTS: Horizontally orientated BT image volumes were read faster than vertically when using free scroll browsing only and when combined with fast cine loop. Cine loops at slow frame rates were ruled out as inefficient. CONCLUSIONS: In general, horizontally oriented BT image volumes were read more efficiently. All viewing procedures except for slow frame rates were promising when assuming equivalent detection performance. KEY POINTS : • Breast tomosynthesis is increasingly used for breast cancer detection • There is a benefit in reading breast tomosynthesis image volumes presented horizontally • Align image content to visual field, especially for dynamic 3D images • Reading at slow frame rates was considered inefficient.
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42.
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43.
  • Timberg, Pontus, et al. (author)
  • Visibility of single spiculations in digital breast tomosynthesis
  • 2013
  • In: Medical Imaging 2013: Image Perception, Observer Performance, And Technology Assessment. - : SPIE. - 0277-786X .- 1996-756X. ; 8673, s. 86731-86731
  • Conference paper (peer-reviewed)abstract
    • 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.
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44.
  • Tingberg, Anders, et al. (author)
  • Breast Cancer Screening With Tomosynthesis-Initial Experiences
  • 2011
  • In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 147:1-2, s. 180-183
  • Journal article (peer-reviewed)abstract
    • Experiences gained so far using tomosynthesis for breast cancer screening will be reported. A short summary of results from preparatory studies will also be presented. The sensitivity and specificity of breast tomosynthesis (BT) will be compared with conventional two-dimensional digital mammography (DM) for breast cancer screening in a population-based study. Over 2000 women have been examined so far with BT and DM. The BT reading is significantly more time-consuming than the DM reading. Preparatory studies have shown that BT has a higher diagnostic precision and higher accuracy of size measurements and stage determination than DM. There is potential to use lower compression force with BT compared with DM, without decreasing the diagnostic accuracy. BT might play an important role in clinical as well as screening mammography. A large-scale population-based study to investigate BT as a screening modality is underway.
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45.
  • Tomic, Hanna, et al. (author)
  • Assessment of a tumour growth model for virtual clinical trials of breast cancer screening
  • 2021
  • In: Medical Imaging 2021 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 1605-7422. - 9781510640191 ; 11595
  • Conference paper (peer-reviewed)abstract
    • Image-based analysis of breast tumour growth rate may help optimize breast cancer screening and diagnosis. It may improve the identification of aggressive tumours and suggest optimal screening intervals. Virtual clinical trial (VCT) is a simulation-based method used to evaluate and optimize medical imaging systems and design clinical trials. Our work is motivated by desire to simulate multiple screening rounds with growing tumours. We have developed a model to simulate tumours with various growth rates; this study aims at evaluating the model. We used clinical data on tumour volume doubling times (TVDT) from our previous study, to fit a probability distribution ("clinical fit"). Growing tumours were inserted into 30 virtual breasts ("simulated cohort"). Based on the clinical fit we simulated two successive screening rounds for each virtual breast. TVDT from clinical and simulated images were compared. Tumour size was measured from simulated mammograms by a radiologist in three repeated sessions, to estimate TVDT ("estimated TVDT"). Reproducibility of measured sizes decreased slightly for small tumours. The mean TVDT from the clinical fit was 297±169 days, whereas the simulated cohort had 322±217 days, and the average estimated TVDT 340 ± 287 days. The median difference between the simulated and estimated TVDT was 12 days (4% of the mean clinical TVDT). Comparisons between other data sets suggest no significant difference (p>0.5). The proposed tumour growth model suggested close agreement with clinical results, supporting potential use in VCTs of temporal breast imaging.
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46.
  • Tomic, Hanna, et al. (author)
  • Development and evaluation of a method for tumor growth simulation in virtual clinical trials of breast cancer screening
  • 2022
  • In: Journal of Medical Imaging. - 2329-4302. ; 9:3
  • Journal article (peer-reviewed)abstract
    • Purpose: Image-based analysis of breast tumor growth rate may optimize breast cancer screening and diagnosis by suggesting optimal screening intervals and guide the clinical discussion regarding personalized screening based on tumor aggressiveness. Simulation-based virtual clinical trials (VCTs) can be used to evaluate and optimize medical imaging systems and design clinical trials. This study aimed to simulate tumor growth over multiple screening rounds. Approach: This study evaluates a preliminary method for simulating tumor growth. Clinical data on tumor volume doubling time (TVDT) was used to fit a probability distribution ("clinical fit") of TVDTs. Simulated tumors with TVDTs sampled from the clinical fit were inserted into 30 virtual breasts ("simulated cohort") and used to simulate mammograms. Based on the TVDT, two successive screening rounds were simulated for each virtual breast. TVDTs from clinical and simulated mammograms were compared. Tumor sizes in the simulated mammograms were measured by a radiologist in three repeated sessions to estimate TVDT. Results: The mean TVDT was 297 days (standard deviation, SD, 169 days) in the clinical fit and 322 days (SD, 217 days) in the simulated cohort. The mean estimated TVDT was 340 days (SD, 287 days). No significant difference was found between the estimated TVDTs from simulated mammograms and clinical TVDT values (p > 0.5). No significant difference (p > 0.05) was observed in the reproducibility of the tumor size measurements between the two screening rounds. Conclusions: The proposed method for tumor growth simulation has demonstrated close agreement with clinical results, supporting potential use in VCTs of temporal breast imaging.
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47.
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48.
  • Tomic, Hanna, et al. (author)
  • Tumor growth rate estimations in a breast cancer screening population
  • 2022
  • In: 16th International Workshop on Breast Imaging, IWBI 2022. - : SPIE. - 0277-786X .- 1996-756X. - 9781510655843 ; 12286
  • Conference paper (peer-reviewed)abstract
    • Tumor growth rate estimations can provide useful information about tumor progression and aggressiveness. Understanding the breast cancer progression and aggressiveness could aid with personalized screening/follow-up, treatment options, and prognosis. This paper reports a preliminary estimation of the tumor volume doubling time (TVDT) for cancers detected during the Malmö Breast Tomosynthesis Screening Trial (MBTST). The trial included 14 848 women in whom 139 cancers were detected. Out of those, 101 spiculated or circumscribed masses, had prior images available, making them suitable for tumor growth evaluation. In the preliminary analysis of images from 30 women, tumor size was measured in mammograms from MBTST and prior images. The analyzed cases were selected among women with visible tumors in two consecutive screening exams. The tumor size was measured in two orthogonal directions. The average of the two measurements was used in the analysis. The mean time and the corresponding standard deviation (SD) between the two consecutive mammograms were 744 ± 73 days. The mean TVDT and SD were 637 ± 428 days (range 159-2373 days). Future work will include the analysis of a larger number of women and a stratification of TVDT related to screening intervals.
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