P. Baltzer

Clinical application of bilateral high temporal and spatial resolution dynamic contrast-enhanced magnetic resonance imaging of the breast at 7 T

ObjectiveThe objective of our study was to evaluate the clinical application of bilateral high spatial and temporal resolution dynamic contrast-enhanced magnetic resonance imaging (HR DCE-MRI) of the breast at 7xa0T.MethodsFollowing institutional review board approval 23 patients with a breast lesion (BIRADS 0, 4–5) were included in our prospective study. All patients underwent bilateral HR DCE-MRI of the breast at 7xa0T (spatial resolution of 0.7xa0mm3 voxel size, temporal resolution of 14xa0s). Two experienced readers (r1, r2) and one less experienced reader (r3) independently assessed lesions according to BI-RADS®. Image quality, lesion conspicuity and artefacts were graded from 1 to 5. Sensitivity, specificity and diagnostic accuracy were assessed using histopathology as the standard of reference.ResultsHR DCE-MRI at 7xa0T revealed 29 lesions in 23 patients (sensitivity 100xa0% (19/19); specificity of 90xa0% (9/10)) resulting in a diagnostic accuracy of 96.6xa0% (28/29) with an AUC of 0.95. Overall image quality was excellent in the majority of cases (27/29) and examinations were not hampered by artefacts. There was excellent inter-reader agreement for diagnosis and image quality parameters (κu2009=u20090.89–1).ConclusionBilateral HR DCE-MRI of the breast at 7xa0T is feasible with excellent image quality in clinical practice and allows accurate breast cancer diagnosis.Key points• Dynamic contrast-enhanced 7-T MRI is being developed in several centres.• Bilateral high resolution DCE-MRI of the breast at 7xa0T is clinically applicable.• 7-T HR DCE-MRI of the breast provides excellent image quality.• 7-T HR DCE-MRI should detect breast cancer with high diagnostic accuracy.

Fat saturation in dynamic breast MRI at 3 Tesla: is the Dixon technique superior to spectral fat saturation? A visual grading characteristics study.

AbstractPurposeTo intra-individually compare the diagnostic image quality of Dixon and spectral fat suppression at 3xa0T.MethodsFifty consecutive patients (mean age 55.1xa0years) undergoing 3 T breast MRI were recruited for this prospective study. The image protocol included pre-contrast and delayed post-contrast spectral and Dixon fat-suppressed T1w series. Two independent blinded readers compared spectral and Dixon fat-suppressed series by evaluating six ordinal (1 worst to 5 best) image quality criteria (image quality, delineation of anatomical structures, fat suppression in the breast and axilla, lesion delineation and internal enhancement). Breast density and size were assessed. Data analysis included Spearman’s rank correlation coefficient and visual grading characteristics (VGC) analysis.ResultsFour examinations were excluded; 48 examinations in 46 patients were evaluated. In VGC analysis, the Dixon technique was superior regarding image quality criteria analysed (Pu2009<u20090.01). Smaller breast size and lower breast density were significantly (Pu2009<u20090.01) correlated with impaired spectral fat suppression quality. No such correlation was identified for the Dixon technique, which showed reconstruction-based water-fat mixups leading to insufficient image quality in 20.8xa0%.ConclusionsThe Dixon technique outperformed spectral fat suppression in all evaluated criteria (Pu2009<u20090.01). Non-diagnostic examinations can be avoided by fat and water image reconstruction. The superior image quality of the Dixon technique can improve breast MRI interpretation.Key Points• Optimal fat suppression quality is necessary for optimal image interpretationn • Superior fat suppression quality is achieved using the Dixon techniquen • Lesion margin and internal enhancement evaluation improves using the Dixon techniquen • Superior image quality of the Dixon technique improves breast MRI interpretation

DCE-MRI of the breast in a stand-alone setting outside a complementary strategy - results of the TK-study

AbstractObjectivesTo evaluate the accuracy of MRI of the breast (DCE-MRI) in a stand-alone setting with extended indications.Materials and methodsAccording to the inclusion criteria, breast specialists were invited to refer patients to our institution for DCE-MRI. Depending on the MR findings, patients received either a follow-up or biopsy. Between 04/2006 and 12/2011 a consecutive total of 1,488 women were prospectively examined.ResultsOf 1,488 included patients, 393 patients were lost to follow-up, 1,095 patients were evaluated. 124 patients were diagnosed with malignancy by DCE-MRI (76 TP, 48 FP, 971 TN, 0 FN cases). Positive cases were confirmed by histology, negative cases by MR follow-ups or patient questionnaires over the next 5xa0years in 1,737 cases (sensitivity 100xa0%; specificity 95.2xa0%; PPV 61.3xa0%; NPV 100xa0%; accuracy 95.5xa0%). For invasive cancers only (DCIS excluded), the results were 63 TP; 27 FP; 971 TP and 0 FN (sensitivity 100xa0%; specificity 97.2xa0%; PPV 70xa0%; NPV 100xa0%; accuracy 97.5xa0%).ConclusionThe DCE-MRI indications tested imply that negative results in DCE-MRI reliably exclude cancer. The results were achieved in a stand-alone setting (single modality diagnosis). However, these results are strongly dependent on reader experience and adequate technical standards as prerequisites for optimal diagnoses.Key Points• DCE-MRI of the breast has a high accuracy in finding breast cancer.n • The set of indications for DCE-MRI of the breast is still very limited.n • DCE-MRI can achieve a high accuracy in a ‘screening-like’ setting.n • Accuracy of breast DCE-MRI is strongly dependent on technique and reader experience.n • A negative DCE-MRI effectively excludes cancer.

Diffusion-weighted imaging of breast tumours at 3 Tesla and 7 Tesla: a comparison.

ObjectivesTo compare bilateral diffusion-weighted MR imaging (DWI) at 3xa0T and 7xa0T in the same breast tumour patients.MethodsTwenty-eight patients were included in this IRB-approved study (mean age 56u2009±u200916xa0years). Before contrast-enhanced imaging, bilateral DWI with bu2009=u20090 and 850xa0s/mm2 was performed in 2:56xa0min (3xa0T) and 3:48xa0min (7xa0T), using readout-segmented echo planar imaging (rs-EPI) with a 1.4u2009×u20091.4xa0mm2 (3xa0T)/0.9u2009×u20090.9xa0mm2 (7xa0T) in-plane resolution. Apparent diffusion coefficients (ADC), signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were assessed.ResultsTwenty-eight lesions were detected (18 malignant, 10 benign). CNR and SNR were comparable at both field strengths (pu2009>u20090.3). Mean ADC values at 7xa0T were 4–22xa0% lower than at 3xa0T (pu2009≤u20090.03). An ADC threshold of 1.275u2009×u200910−3xa0mm2/s resulted in a diagnostic specificity of 90xa0% at both field strengths. The sensitivity was 94xa0% and 100xa0% at 3xa0T and 7xa0T, respectively.Conclusion7-T DWI of the breast can be performed with 2.4-fold higher spatial resolution than 3xa0T, without significant differences in SNR if compared to 3xa0T.Key points• 7xa0T provides a 2.4-fold higher resolution in breast DWI than 3xa0T• 7xa0T DWI has a high diagnostic accuracy comparable to that at 3xa0T• At 7xa0T malignant lesions had 22xa0% lower ADC than at 3xa0T (pu2009<u20090.001)

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 (ku2009=u20090.209–0.497) 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.n • Automated observer-independent quantitative measurements can provide reliable and standardized assessment of FGT with MRI.

Molecular breast imaging. An update

CLINICAL/METHODICAL ISSUEnThe aim of molecular imaging is to visualize and quantify biological, physiological and pathological processes at cellular and molecular levels. Molecular imaging using various techniques has recently become established in breast imaging.nnnSTANDARD RADIOLOGICAL METHODSnCurrently molecular imaging techniques comprise multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), proton MR spectroscopy ((1)H-MRSI), nuclear imaging by breast-specific gamma imaging (BSGI), positron emission tomography (PET) and positron emission mammography (PEM) and combinations of techniques (e.g. PET-CT and multiparametric PET-MRI).nnnMETHODICAL INNOVATIONSnRecently, novel techniques for molecular imaging of breast tumors, such as sodium imaging ((23)Na-MRI), phosphorus spectroscopy ((31)P-MRSI) and hyperpolarized MRI as well as specific radiotracers have been developed and are currently under investigation.nnnPRACTICAL RECOMMENDATIONSnIt can be expected that molecular imaging of breast tumors will enable a simultaneous assessment of the multiple metabolic and molecular processes involved in cancer development and thus an improved detection, characterization, staging and monitoring of response to treatment will become possible.ZusammenfassungKlinisches/methodisches ProblemDie molekulare Bildgebung zielt auf die Darstellung, Beschreibung und Quantifizierung biologischer, physiologischer und pathologischer Prozesse auf zellulärer und molekularer Ebene ab. In den letzten Jahren hat sich die molekulare Bildgebung mit ihren verschiedenen Modalitäten in der Brustdiagnostik etabliert.Radiologische StandardverfahrenDie molekularen Brustbildgebung umfasst derzeit die multiparametrische(MP)-MRT mit funktioneller und morphologischer kontrastmittelverstärkter MRT (KM-MRT), molekularer diffusionsgewichteter Bildgebung („diffusion-weighted imaging“, DWI) und metabolischer Protonenspektroskopie (1H-MRSI) sowie nuklearmedizinische Verfahren (brustspezifische Gammakamerabildgebung [BSGI], Positronenemissionstomographie [PET], PET-Mammographie [PEM]) und kombinierte Verfahren (PET-CT, MP-PET-MRT).Methodische InnovationenDie molekulare Bildgebung in der Mammadiagnostik ist ein sich rapide entwickelndes Forschungsfeld mit neuen vielversprechenden Techniken wie der Natriumbildgebung (23Na-MRT), der Phosphorspektroskopie (31P-MRSI) und der hyperpolarisierten MRT sowie neuen zielgerichteten Radiotracern und Kontrastmitteln.BewertungDer Einfluss der molekularen Brustbildgebung wird in den nächsten Jahren weiter zunehmen. Es ist zu erwarten, dass durch die molekulare Brustbildgebung eine optimierte Detektion und Charakterisierung von Brusttumoren, ein akkurates lokales und peripheres Staging sowie eine zielgerichtete Therapieverlaufskontrolle ermöglicht werden wird.AbstractClinical/methodical issueThe aim of molecular imaging is to visualize and quantify biological, physiological and pathological processes at cellular and molecular levels. Molecular imaging using various techniques has recently become established in breast imaging.Standard radiological methodsCurrently molecular imaging techniques comprise multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), proton MR spectroscopy (1H-MRSI), nuclear imaging by breast-specific gamma imaging (BSGI), positron emission tomography (PET) and positron emission mammography (PEM) and combinations of techniques (e.g. PET-CT and multiparametric PET-MRI).Methodical innovationsRecently, novel techniques for molecular imaging of breast tumors, such as sodium imaging (23Na-MRI), phosphorus spectroscopy (31P-MRSI) and hyperpolarized MRI as well as specific radiotracers have been developed and are currently under investigation.Practical recommendationsIt can be expected that molecular imaging of breast tumors will enable a simultaneous assessment of the multiple metabolic and molecular processes involved in cancer development and thus an improved detection, characterization, staging and monitoring of response to treatment will become possible.

Density and tailored breast cancer screening: practice and prediction – an overview:

Mammography, as the primary screening modality, has facilitated a substantial decrease in breast cancer-related mortality in the general population. However, the sensitivity of mammography for breast cancer detection is decreased in women with higher breast densities, which is an independent risk factor for breast cancer. With increasing public awareness of the implications of a high breast density, there is an increasing demand for supplemental screening in these patients. Yet, improvements in breast cancer detection with supplemental screening methods come at the expense of increased false-positives, recall rates, patient anxiety, and costs. Therefore, breast cancer screening practice must change from a general one-size-fits-all approach to a more personalized, risk-based one that is tailored to the individual woman’s risk, personal beliefs, and preferences, while accounting for cost, potential harm, and benefits. This overview will provide an overview of the available breast density assessment modalities, the current breast density screening recommendations for women at average risk of breast cancer, and supplemental methods for breast cancer screening. In addition, we will provide a look at the possibilities for a risk-adapted breast cancer screening.

Motion artifacts, lesion type, and parenchymal enhancement in breast MRI: what does really influence diagnostic accuracy?

Background Motion artifacts can reduce image quality of breast magnetic resonance imaging (MRI). There is a lack of data regarding their effect on diagnostic estimates. Purpose To evaluate factors that potentially influence readers’ diagnostic estimates in breast MRI: motion artifacts; amount of fibroglandular tissue; background parenchymal enhancement; lesion size; and lesion type. Material and Methods This Institutional Review Board-approved, retrospective, cross-sectional, single-center study included 320 patients (mean ageu2009=u200955.1 years) with 334 histologically verified breast lesions (139 benign, 195 malignant) who underwent breast MRI. Two expert breast radiologists evaluated the images considering: motion artifacts (1u2009=u2009minimal to 4u2009=u2009marked); fibroglandular tissue (BI-RADS FGT); background parenchymal enhancement (BI-RADS BPE); lesion size; lesion type; and BI-RADS score. Univariate (Chi-square) and multivariate (Generalized Estimation Equations [GEE]) statistics were used to identify factors influencing sensitivity, specificity, and accuracy. Results Lesions were: 230 mass (68.9%) and 59 non-mass (17.7%), no foci. Forty-five lesions (13.5%) did not enhance in MRI but were suspicious or unclear in conventional imaging. Sensitivity, specificity, and accuracy were 93.8%, 83.4%, and 89.8% for Reader 1 and 95.4%, 87.8%, and 91.9% for Reader 2. Lower sensitivity was observed in case of increased motion artifacts (Pu2009=u20090.007), non-mass lesions (Pu2009<u20090.001), and small lesionsu2009≤u200910u2009mm (Pu2009<u20090.021). No further factors (e.g. BPE, FGT) significantly influenced diagnostic estimates. At multivariate analysis, lesion type and size were retained as independent factors influencing the diagnostic performance (Pu2009<u20090.033). Conclusion Motion artifacts can impair lesion characterization with breast MRI, but lesion type and small size have the strongest influence on diagnostic estimates.

Use Case III: Imaging Biomarkers in Breast Tumours. Development and Clinical Integration

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide [1]. It is a heterogeneous disease with distinct molecular and genetic subtypes, each with characteristic clinical-biological behavior and imaging patterns. A substantial proportion of tumor markers or biomarkers, both fluid and tissue based, are currently used in the management of patients with breast cancer. Serum biomarkers, such as CA 15–3 and carcinoembryonic antigen (CEA), are not recommended in any senological guidelines due to a lack of sensitivity for early disease and a lack of specificity [2]. Rather, genetic tests are regularly performed in populations at high risk of developing breast cancer. By means of a minimally invasive blood test, women are told whether a germ line mutation in cancer susceptibility genes is present (BRCA). Being diagnosed with a BRCA 1 or 2 gene mutation has a dramatic impact on the life course of a woman. About 5–10 % of all breast cancers are caused by germ line mutations in the two breast cancer susceptibility genes, BRCA-1 and BRCA-2, and women carrying BRCA1 or BRCA2 mutations have an increased risk of developing breast cancer of approximately 50–80 % at 70 years of age [3–5]. Various histopathological and immunohistochemical staining-derived features of breast cancer are used to clinically establish the prognostically relevant subtype, including hormonal receptor expression, architectural growth patterns, and nuclear grades (low, intermediate, or high). Subsequently, the individual management of breast cancer patients is adapted according to these subtypes. Despite the enormous advances in breast imaging, the aforementioned clinically relevant subtyping of breast lesions is still based on invasive procedures, such as core needle biopsy or surgery. However, imaging is increasingly used to assess not only the morphologic features of the pathological process but also to assess the function of tumor tissues or to characterize individual phenotypes for targeted drug therapies, building on developments in genomics and molecular biology features [6–9]. Imaging biomarkers can be defined as any anatomic, physiologic, biochemical, or molecular parameter that is detectable with one or more imaging methods used to help establish the presence and/or severity of disease. The specific term “quantitative imaging biomarkers” corresponds to parameters that are objectively and quantitatively measured noninvasively, are less susceptible to subjective judgment, and are resolved spatially and temporally [10]. Moreover, prerequisites for the effective use of imaging biomarkers are standardization and validation [10–12]. The aim of this chapter is to describe breast imaging biomarkers and their objective, quantifiable features. We consider here only imaging biomarkers that require an element of quantification and standardization, to demonstrate their contribution in the management of breast cancer patients. First, we briefly summarize the heterogeneous group of subtypes of breast cancer, both invasive and noninvasive, to give the reader a synopsis of the complexity of this disease and an insight into the molecular biomarkers of breast cancer. However, a complete overview of the different histologic breast cancer subtypes is beyond the aim of this chapter. Second, we discuss the role of breast imaging biomarkers in terms of risk prediction for the development of breast cancer. These include quantitative imaging techniques for the assessment of breast density based on mammography and the measure of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) based on magnetic resonance imaging (MRI). Third, we will explain the central role of MRI in noninvasively providing quantitative information about tissue characteristics, such as cell density, tumor angiogenesis, and metabolism, leading to an improved differentiation of benign and malignant breast lesions and to a better management of breast cancer patients in monitoring and predicting response to treatment. Finally, we discuss the potential of other imaging techniques, and emerging techniques, which could improve diagnostic accuracy and have the potential for the development of new imaging biomarkers.