Georg Wengert

Introduction of an automated user-independent quantitative volumetric magnetic resonance imaging breast density measurement system using the Dixon sequence: comparison with mammographic breast density assessment.

ObjectivesThe purposes of this study were to introduce and assess an automated user-independent quantitative volumetric (AUQV) breast density (BD) measurement system on the basis of magnetic resonance imaging (MRI) using the Dixon technique as well as to compare it with qualitative and quantitative mammographic (MG) BD measurements. Materials and MethodsForty-three women with normal mammogram results (Breast Imaging Reporting and Data System 1) were included in this institutional review board–approved prospective study. All participants were subjected to BD assessment with MRI using the following sequence with the Dixon technique (echo time/echo time, 6 milliseconds/2.45 milliseconds/2.67 milliseconds; 1-mm isotropic; 3 minutes 38 seconds). To test the reproducibility, a second MRI after patient repositioning was performed. The AUQV magnetic resonance (MR) BD measurement system automatically calculated percentage (%) BD. The qualitative BD assessment was performed using the American College of Radiology Breast Imaging Reporting and Data System BD categories. Quantitative BD was estimated semiautomatically using the thresholding technique Cumulus4. Appropriate statistical tests were used to assess the agreement between the AUQV MR measurements and to compare them with qualitative and quantitative MG BD estimations. ResultsThe AUQV MR BD measurements were successfully performed in all 43 women. There was a nearly perfect agreement of AUQV MR BD measurements between the 2 MR examinations for % BD (P < 0.001; intraclass correlation coefficient, 0.998) with no significant differences (P = 0.384). The AUQV MR BD measurements were significantly lower than quantitative and qualitative MG BD assessment (P < 0.001). ConclusionsThe AUQV MR BD measurement system allows a fully automated, user-independent, robust, reproducible, as well as radiation- and compression-free volumetric quantitative BD assessment through different levels of BD. The AUQV MR BD measurements were significantly lower than the currently used qualitative and quantitative MG-based approaches, implying that the current assessment might overestimate breast density with MG.

Diffusion-weighted imaging of breast lesions: Region-of-interest placement and different ADC parameters influence apparent diffusion coefficient values

ObjectivesTo investigate the influence of region-of-interest (ROI) placement and different apparent diffusion coefficient (ADC) parameters on ADC values, diagnostic performance, reproducibility and measurement time in breast tumours.MethodsIn this IRB-approved, retrospective study, 149 histopathologically proven breast tumours (109 malignant, 40 benign) in 147 women (mean age 53.2) were investigated. Three radiologists independently measured minimum, mean and maximum ADC, each using three ROI placement approaches:1 – small 2D-ROI, 2 – large 2D-ROI and 3 – 3D-ROI covering the whole lesion. One reader performed all measurements twice. Median ADC values, diagnostic performance, reproducibility, and measurement time were calculated and compared between all combinations of ROI placement approaches and ADC parameters.ResultsMedian ADC values differed significantly between the ROI placement approaches (p < .001). Minimum ADC showed the best diagnostic performance (AUC .928–.956), followed by mean ADC obtained from 2D ROIs (.926–.94). Minimum and mean ADC showed high intra- (ICC .85–.94) and inter-reader reproducibility (ICC .74–.94). Median measurement time was significantly shorter for the 2D ROIs (p < .001).ConclusionsROI placement significantly influences ADC values measured in breast tumours. Minimum and mean ADC acquired from 2D-ROIs are useful for the differentiation of benign and malignant breast lesions, and are highly reproducible, with rapid measurement.Key Points• Region of interest placement significantly influences apparent diffusion coefficient of breast tumours.• Minimum and mean apparent diffusion coefficient perform best and are reproducible.• 2D regions of interest perform best and provide rapid measurement times.

Molecular imaging for the characterization of breast tumors

Recently, molecular imaging, using various techniques, has been assessed for breast imaging. Molecular imaging aims to quantify and visualize biological, physiological, and pathological processes at the cellular and molecular levels to further elucidate the development and progression of breast cancer and the response to treatment. Molecular imaging enables the depiction of tumor morphology, as well as the assessment of functional and metabolic processes involved in cancer development at different levels. To date, molecular imaging techniques comprise both nuclear medicine and radiological techniques. This review aims to summarize the current and emerging functional and metabolic techniques for the molecular imaging of breast tumors.

Inter- and intra-observer agreement of BI-RADS-based subjective visual estimation of amount of fibroglandular breast tissue with magnetic resonance imaging: comparison to automated quantitative assessment

AbstractPurposeTo evaluate the inter-/intra-observer agreement of BI-RADS-based subjective visual estimation of the amount of fibroglandular tissue (FGT) with magnetic resonance imaging (MRI), and to investigate whether FGT assessment benefits from an automated, observer-independent, quantitative MRI measurement by comparing both approaches.Materials and methodsEighty women with no imaging abnormalities (BI-RADS 1 and 2) were included in this institutional review board (IRB)-approved prospective study. All women underwent un-enhanced breast MRI. Four radiologists independently assessed FGT with MRI by subjective visual estimation according to BI-RADS. Automated observer-independent quantitative measurement of FGT with MRI was performed using a previously described measurement system. Inter-/intra-observer agreements of qualitative and quantitative FGT measurements were assessed using Cohen’s kappa (k).ResultsInexperienced readers achieved moderate inter-/intra-observer agreement and experienced readers a substantial inter- and perfect intra-observer agreement for subjective visual estimation of FGT. Practice and experience reduced observer-dependency. Automated observer-independent quantitative measurement of FGT was successfully performed and revealed only fair to moderate agreement (k = 0.209–0.497) with subjective visual estimations of FGT.ConclusionSubjective visual estimation of FGT with MRI shows moderate intra-/inter-observer agreement, which can be improved by practice and experience. Automated observer-independent quantitative measurements of FGT are necessary to allow a standardized risk evaluation.Key Points• Subjective FGT estimation with MRI shows moderate intra-/inter-observer agreement in inexperienced readers.• Inter-observer agreement can be improved by practice and experience. • Automated observer-independent quantitative measurements can provide reliable and standardized assessment of FGT with MRI.

Dynamical graph theory networks techniques for the analysis of sparse connectivity networks in dementia

Graph network models in dementia have become an important computational technique in neuroscience to study fundamental organizational principles of brain structure and function of neurodegenerative diseases such as dementia. The graph connectivity is reflected in the connectome, the complete set of structural and functional connections of the graph network, which is mostly based on simple Pearson correlation links. In contrast to simple Pearson correlation networks, the partial correlations (PC) only identify direct correlations while indirect associations are eliminated. In addition to this, the state-of-the-art techniques in brain research are based on static graph theory, which is unable to capture the dynamic behavior of the brain connectivity, as it alters with disease evolution. We propose a new research avenue in neuroimaging connectomics based on combining dynamic graph network theory and modeling strategies at different time scales. We present the theoretical framework for area aggregation and time-scale modeling in brain networks as they pertain to disease evolution in dementia. This novel paradigm is extremely powerful, since we can derive both static parameters pertaining to node and area parameters, as well as dynamic parameters, such as system’s eigenvalues. By implementing and analyzing dynamically both disease driven PC-networks and regular concentration networks, we reveal differences in the structure of these network that play an important role in the temporal evolution of this disease. The described research is key to advance biomedical research on novel disease prediction trajectories and dementia therapies.

Accuracy of fully automated, quantitative, volumetric measurement of the amount of fibroglandular breast tissue using MRI: correlation with anthropomorphic breast phantoms

To demonstrate the accuracy of fully automated, quantitative, volumetric measurement of the amount of fibroglandular breast tissue (FGT), using MRI, and to investigate the impact of different MRI sequences using anthropomorphic breast phantoms as the ground truth.

Quantitative Assessment of Breast Parenchymal Uptake on 18F-FDG PET/CT: Correlation with Age, Background Parenchymal Enhancement, and Amount of Fibroglandular Tissue on MRI

Background parenchymal enhancement (BPE), and the amount of fibroglandular tissue (FGT) assessed with MRI have been implicated as sensitive imaging biomarkers for breast cancer. The purpose of this study was to quantitatively assess breast parenchymal uptake (BPU) on 18F-FDG PET/CT as another valuable imaging biomarker and examine its correlation with BPE, FGT, and age. Methods: This study included 129 patients with suspected breast cancer and normal imaging findings in one breast (BI-RADS 1), whose cases were retrospectively analyzed. All patients underwent prone 18F-FDG PET/CT and 3-T contrast-enhanced MRI of the breast. In all patients, interpreter 1 assessed BPU quantitatively using SUVmax. Interpreters 1 and 2 assessed amount of FGT and BPE in the normal contralateral breast by subjective visual estimation, as recommended by BI-RADS. Interpreter 1 reassessed all cases and repeated the BPU measurements. Statistical tests were used to assess correlations between BPU, BPE, FGT, and age, as well as inter- and intrainterpreter agreement. Results: BPU on 18F-FDG PET/CT varied among patients. The mean BPU SUVmax ± SD was 1.57 ± 0.6 for patients with minimal BPE, 1.93 ± 0.6 for mild BPE, 2.42 ± 0.5 for moderate BPE, and 1.45 ± 0.3 for marked BPE. There were significant (P < 0.001) moderate to strong correlations among BPU, BPE, and FGT. BPU directly correlated with both BPE and FGT on MRI. Patient age showed a moderate to strong indirect correlation with all 3 imaging-derived tissue biomarkers. The coefficient of variation for quantitative BPU measurements with SUVmax was 5.6%, indicating a high reproducibility. Interinterpreter and intrainterpreter agreement for BPE and FGT was almost perfect, with a κ-value of 0.860 and 0.822, respectively. Conclusion: The results of our study demonstrate that BPU varied among patients. BPU directly correlated with both BPE and FGT on MRI, and BPU measurements were highly reproducible. Patient age showed a strong inverse correlation with all 3 imaging-derived tissue biomarkers. These findings indicate that BPU may serve as a sensitive imaging biomarker for breast cancer prediction, prognosis, and risk assessment.

Influence of fat-water separation and spatial resolution on automated volumetric MRI measurements of fibroglandular breast tissue.

The aim of this study was to investigate the influence of fat–water separation and spatial resolution in MRI on the results of automated quantitative measurements of fibroglandular breast tissue (FGT). Ten healthy volunteers (age range, 28–71 years; mean, 39.9 years) were included in this Institutional Review Board‐approved prospective study. All measurements were performed on a 1.5‐T scanner (Siemens, AvantoFit) using an 18‐channel breast coil. The protocols included isotropic (Di) [TR/TE1/TE2 = 6.00 ms/2.45 ms/2.67 ms; flip angle, 6.0°; 256 slices; matrix, 360 × 360; 1 mm isotropic; field of view, 360°; acquisition time (TA) = 3 min 38 s] and anisotropic (Da) (TR/TE1/TE2 = 10.00 ms/2.39 ms/4.77 ms; flip angle, 24.9°; 80 slices; matrix 360 × 360; voxel size, 0.7 × 0.7 × 2.0 mm3; field of view, 360°; TA = 1 min 25 s) T1 three‐dimensional (3D) fast low‐angle shot (FLASH) Dixon sequences, and a T1 3D FLASH sequence with the same resolution (T1) without (TR/TE = 11.00 ms/4.76 ms; flip angle, 25.0°; 80 slices; matrix, 360 × 360; voxel size, 0.7 × 0.7 × 2.0 mm3; field of view, 360°; TA = 50 s) and with (TR/TE = 29.00 ms/4.76 ms; flip angle, 25.0°; 80 slices; matrix, 360 × 360; voxel size, 0.7 × 0.7 × 2.0 mm3; field of view, 360°; TA = 2 min 35 s) fat saturation. Repeating volunteer measurements after 20 min and repositioning were used to assess reproducibility. An automated and quantitative volumetric breast density measurement system was used for FGT calculation. FGT with Di, Da and T1 measured 4.6–63.0% (mean, 30.6%), 3.2–65.3% (mean, 32.5%) and 1.7–66.5% (mean, 33.7%), respectively. The highest correlation between different MRI sequences was found with the Di and Da sequences (R2 = 0.976). Coefficients of variation (CVs) for FGT calculation were higher in T1 (CV = 21.5%) compared with Dixon (Di, CV = 5.1%; Da, CV = 4.2%) sequences. Dixon‐type sequences worked well for FGT measurements, even at lower resolution, whereas the conventional T1‐weighted sequence was more sensitive to decreasing resolution. The Dixon fat–water separation technique showed superior repeatability of FGT measurements compared with conventional sequences. A standard dynamic protocol using Dixon fat–water separation is best suited for combined diagnostic purposes and prognostic measurements of FGT. Copyright

Clinical role of breast MRI now and going forward

Magnetic resonance imaging (MRI) is a well-established method in breast imaging, with manifold clinical applications, including the non-invasive differentiation between benign and malignant breast lesions, preoperative staging, detection of scar versus recurrence, implant assessment, and the evaluation of high-risk patients. At present, dynamic contrast-enhanced MRI is the most sensitive imaging technique for breast cancer diagnosis, and provides excellent morphological and to some extent also functional information. To compensate for the limited functional information, and to increase the specificity of MRI while preserving its sensitivity, additional functional parameters such as diffusion-weighted imaging and apparent diffusion coefficient mapping, and MR spectroscopic imaging have been investigated and implemented into the clinical routine. Several additional MRI parameters to capture breast cancer biology are still under investigation. MRI at high and ultra-high field strength and advances in hard- and software may also further improve this imaging technique. This article will review the current clinical role of breast MRI, including multiparametric MRI and abbreviated protocols, and provide an outlook on the future of this technique. In addition, the predictive and prognostic value of MRI as well as the evolving field of radiogenomics will be discussed.

Determining the importance of parameters extracted from multi-parametric MRI in the early prediction of the response to neo-adjuvant chemotherapy in breast cancer

Neo-adjuvant chemotherapy (NAC) is the treatment of choice in patients with locally advanced breast cancer to reduce tumor burden, and potentially enable breast conservation. Response to treatment is assessed by histopathology from surgical specimen, a pathological complete response (pCR), or a minimal residual disease are associated with an improved disease-free, and overall survival. Early identification of non-responders is crucial as these patients might require different, or more aggressive treatment. Multi-parametric magnetic resonance imaging (mpMRI) using different morphological and functional MRI parameters such as T2-weighted, dynamic contrast-enhanced (DCE) MRI, and diffusion weighted imaging (DWI) has emerged as the method of choice for the early response assessments to NAC. Although, mpMRI is superior to conventional mammography for predicting treatment response, and evaluating residual disease, yet there is still room for improvement. In the past decade, the field of medical imaging analysis has grown exponentially, with an increased numbers of pattern recognition tools, and an increase in data sizes. These advances have heralded the field of radiomics. Radiomics allows the high-throughput extraction of the quantitative features that result in the conversion of images into mineable data, and the subsequent analysis of the data for an improved decision support with response monitoring during NAC being no exception. In this paper, we determine the importance and ranking of the extracted parameters from mpMRI using T2-weighted, DCE, and DWI for prediction of pCR and patient outcomes with respect to metastases and disease-specific death.