Luca A. Carbonaro

Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results.

Objectives:To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. Materials and Methods:We enrolled asymptomatic women aged ≥25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. Results:A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥50 years of age. Conclusion:MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.

Breast Cancer Detection Using Double Reading of Unenhanced MRI Including T1-Weighted, T2- Weighted STIR, and Diffusion- Weighted Imaging: A Proof of Concept Study

OBJECTIVE The purpose of this study was to investigate the diagnostic performance of unenhanced MRI in detecting breast cancer and to assess the impact of double reading. MATERIALS AND METHODS A total of 116 breasts of 67 women who were 36-89 years old were studied at 1.5 T using an unenhanced protocol including axial T1-weighted gradient-echo, T2-weighted STIR, and echo-planar diffusion-weighted imaging (DWI). Two blinded readers (R1 and R2) independently evaluated unenhanced images using the BIRADS scale. A combination of pathology and negative follow-up served as the reference standard. McNemar and kappa statistics were used. RESULTS Per-breast cancer prevalence was 37 of 116 (32%): 30 of 37 (81%) invasive ductal carcinoma, five of 37 (13%) ductal carcinoma in situ, and two of 37 (6%) invasive lobular carcinoma. Per-breast sensitivity of unenhanced MRI was 29 of 37 (78%) for R1, 28 of 37 (76%) for R2, and 29 of 37 (78%) for double reading. Specificity was 71 of 79 (90%) for both R1 and R2 and 69 of 79 (87%) for double reading. Double reading did not provide a significant increase in sensitivity. Interobserver agreement was almost perfect (Cohen κ = 0.873). CONCLUSION An unenhanced breast MRI protocol composed of T1-weighted gradient echo, T2-weighted STIR, and echo-planar DWI enabled breast cancer detection with sensitivity of 76-78% and specificity of 90% without a gain in sensitivity from double reading.

Computer-aided diagnosis for dynamic contrast-enhanced breast MRI of mass-like lesions using a multiparametric model combining a selection of morphological, kinetic, and spatiotemporal features

PURPOSE Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a radiological tool for the detection and discrimination of breast lesions. The aim of this study is to evaluate a computer-aided diagnosis (CAD) system for discriminating malignant from benign breast lesions at DCE-MRI by the combined use of morphological, kinetic, and spatiotemporal lesion features. METHODS Fifty-four malignant and 19 benign breast lesions in 51 patients were retrospectively evaluated. Images were acquired at two centers at 1.5 T. Mass-like lesions were automatically segmented after image normalization and elastic coregistration of contrast-enhanced frames. For each lesion, a set of 28 3D features were extracted: ten morphological (related to shape, margins, and internal enhancement distribution); nine kinetic (computed from signal-to-time curves); and nine spatiotemporal (related to the variation of the signal between adjacent frames). A support vector machine (SVM) was trained with feature subsets selected by a genetic search. Best subsets were composed of the most frequent features selected by majority rule. The performance was measured by receiver operator characteristics analysis with a stratified tenfold cross-validation and bootstrap method for confidence intervals. RESULTS SVM training by the three separated classes of features resulted in an area under the curve (AUC) of 0.90 ± 0.04 (mean ± standard deviation), 0.87 ± 0.06, and 0.86 ± 0.06 for morphological, kinetic, and spatiotemporal feature, respectively. Combined training with all 28 features resulted in AUC of 0.96 ± 0.02 obtained with a selected feature subset composed by two morphological, one kinetic, and two spatiotemporal features. CONCLUSIONS Quantitative combination of morphological, kinetic, and spatiotemporal features is feasible and provides a higher discriminating power than using the three different classes of features separately.

Indications for breast magnetic resonance imaging. Consensus document “Attualità in senologia”, Florence 2007

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.RiassuntoLa RM mammaria è in fase di crescente utilizzo clinico, soprattutto per le applicazioni che richiedono la somministrazione di mezzo di contrasto (MdC) paramagnetico. Il presente documento propone una codificazione sintetica delle indicazioni accettabili con potenziale vantaggio per le donne, secondo la valutazione delle evidenze presenti in letteratura e l’opinione del gruppo di esperti estensori del documento. In generale si raccomanda che l’indagine sia eseguita presso centri che siano in grado di combinare l’esperienza senologica relativa all’imaging convenzionale e ai prelievi agobioptici con quella specifica in RM mammaria e che garantiscano l’esecuzione del second look ecografico per i reperti non rilevati all’imaging convenzionale pre-RM. Non si ritiene che vi siano evidenze in favore dell’utilizzo della RM quale approccio diagnostico nella caratterizzazione di reperti equivoci all’imaging convenzionale in tutte le situazioni nelle quali sia praticabile il prelievo agobioptico sotto guida ecografica o stereotassica né in favore dello studio di donne non ad alto rischio asintomatiche e con imaging convenzionale negativo. Sono qui definiti i requisiti tecnici e metodologici di esecuzione dell’indagine e indicazioni e limiti relativi a: sorveglianza delle donne ad alto rischio di tumore mammario; stadiazione locale pretrattamento chirurgico; valutazione dell’effetto della chemioterapia neoadiuvante; mammella trattata per carcinoma; carcinoma unknown primary syndrome; mammella secernente; protesi mammarie.

Contrast enhanced breast MRI: Spatial displacement from prone to supine patient's position. Preliminary results

OBJECTIVE To estimate the spatial displacement of breast lesions and nipples in MR images when the patient is moved from the standard prone to a supine position close to ultrasound (US) or surgical setting. MATERIALS AND METHODS Eleven patients underwent breast MRI in prone position with dynamic 3D T1-weighted sequences using 0.1 mmol/kg gadobenate dimeglumine. Subsequently, the patient was repositioned in supine position and a 3D volumetric interpolated breathhold examination sequence was acquired using a thoracic surface coil. For both positions we measured the following minimal distances: (A) from lesion margin to the coronal plane passing through the anterior surface of the sternum, antero-posterior, on native axial images; (B) from lesion margin to the medial sagittal plane, on native axial images, latero-medial; (C) from lesion margin to the axial plane passing through the tracheal bifurcation, cranio-caudal; (D) from lesion margin to the thoracic wall/pectoral muscle, on native axial images; (E) from lesion margin to the skin, on native axial images; (F) from lesion margin to the base of the nipple, on oblique reconstructions. Measurements from A to D were also obtained for each nipple. The prone-to-supine spatial displacement was calculated as the absolute difference between the measurement obtained in supine position and the same measurement obtained in prone position. Displacements were presented as mean ± standard deviation and median in parenthesis. RESULTS Lesion displacements were (mm): A = 60 ± 38 (55); B = 40 ± 26 (41); C = 41 ± 33 (34); D = 32 ± 31 (27); E = 6 ± 5 (7); and F = 8 ± 6 (7). Nipple displacements were (mm): A = 84 ± 44 (91); B = 54 ± 24 (56); C = 27 ± 15 (24); and D = 48 ± 20 (48). CONCLUSION These preliminary results show that preoperative breast MRI in prone position implies a median lesion displacement of about 3-6 cm along the three orthogonal directions in comparison with supine MRI. Conversely, median lesion-to-skin and lesion-to-nipple displacements were less than 1cm, even though nipple displacements were similar to or larger than those of lesions. The lesion-to-nipple distance may be the most reliable measure to be used for second look breast US. Larger studies are warranted in order to define an optimized breast MRI protocol in the preoperative setting.

Performance of a fully automatic lesion detection system for breast DCE-MRI.

To describe and test a new fully automatic lesion detection system for breast DCE‐MRI.

A fully automatic algorithm for segmentation of the breasts in DCE-MR images

Automatic segmentation of the breast and axillary region is an important preprocessing step for automatic lesion detection in breast MR and dynamic contrast-enhanced-MR studies. In this paper, we present a fully automatic procedure based on the detection of the upper border of the pectoral muscle. Compared with previous methods based on thresholding, this method is more robust to noise and field inhomogeneities. The method was quantitatively evaluated on 31 cases acquired from two centers by comparing the results with a manual segmentation. Results indicate good overall agreement within the reference segmentation (overlap=0.79±0.09, recall=0.95± 0.02, precision=0.82 ± 0.1).

What is the sensitivity of mammography and dynamic MR imaging for DCIS if the whole-breast histopathology is used as a reference standard?

Purpose. Our purpose was to compare mammography and dynamic contrast-enhanced magnetic resonance imaging (MRI) in the detection of ductal carcinoma in situ (DCIS)Materials and methods. Ninety patients (aged 58.6±16.1 years) who were candidates for unilateral (n=81) or bilateral (n=9) mastectomy underwent mammography and dynamic contrast-enhanced breast MRI using a coronal three-dimensional gradient-echo sequence with slice thickness ≤3 mm before and after intravenous injection of gadoteridol (0.1 mmol/kg). Mammographic and MR images were evaluated by two offsite readers working in consensus. Pathological examination performed on 5-mm sections covering the whole breast was used as a reference standardResults. Out of 99 breasts, pathology revealed 26 DCIS in 14 breasts of 14 patients, aged 52.0+_9.6 years. Lesion diameter at pathology was <5 mm (n=4); ≥5 and <10 mm (n=7); ≥10 and <20 mm (n=3); ≥20 mm (n=2); not assessed (n=10). Sensitivity was 35% (9/26) for mammography and 38% (10/26) for MRI (not significant difference, McNemar test). Both mammography and MRI provided a true positive result in seven cases (four of them measured at pathology, with a diameter of 20.0±12.9 mm; median 20 mm) and a false negative result in 14 cases (10 of them measured at pathology, with a diameter of 4.2±1.9 mm; median 4.6 mm) (p=0.024, Mann-Whitney U test). Only 46% (12/26) of DCIS were detected at mammography and/or MRI; the remaining 54% (14/26) were diagnosed only at pathological examinationConclusions. When the whole breast is used as the histopathological reference standard, both mammography and MRI show low sensitivity for DCISRiassuntoObiettivo . Confrontare la sensibilità per il carcinoma duttale in situ (DCIS) della mammografia e della risonanza magnetica (RM) con mezzo di contrastoMateriali e metodi . Novanta pazienti (età 58.6±16.1 anni) candidate alla mastectomia monolaterale (n=81) o bilaterale (n=9) sono state sottoposte a mammografia e RM a contrasto dinamico mediante sequenza tridimensionale coronale gradient-echo con spessore di strato ≤3 mm, prima e dopo iniezione endovenosa di gadoteridolo (0.1 mmol/kg). Mammografia e RM sono state valutate da due lettori off-site, in consenso. L’;esame istologico dell’;intera mammella (strati di 5 mm di spessore) ha rappresentato lo standard di riferimentoRisultati . L’esame istologico delle 99 mammelle ha evidenziato 26 DCIS in 14 mammelle di 14 pazienti (età 52.0±9.6 anni). All’esame istologico il diametro della lesione è risultato <5 mm (n=4); ≥5 e <10 mm (n=7); ≥10 e <20 mm (n=3); ≥20 mm (n=2); non valutato (n=10). La sensibilità è risultata del 35% (9/26) per la mammografia e del 38% (10/26) per la RM (differenza non significativa, test di McNemar). Mammografia e RM sono risultate entrambe vere positive in 7 casi (4 dei quali con diametro misurato istologicamente, pari a 20.0±12.9 mm, mediana 20 mm) ed entrambe false negative in 14 casi (10 dei quali con diametro misurato istologicamente, pari a 4.2±1.9 mm, mediana 4.6) (p=0.024, test U di Mann-Whitney). Solo il 46% (12/26) dei DCIS sono stati identificati alla mammografia e/o alla RM mentre il rimanente 54% (14/26) è stato riconosciuto solo all’esame istologicoConclusioni . Allorquando l’intera mammella è assunta come standard di riferimento istologico, sia la mammografia che la RM mostrano ridotta sensibilità per il DCIS

Breast Cancer: Computer-aided Detection with Digital Breast Tomosynthesis.

PURPOSE To evaluate a commercial tomosynthesis computer-aided detection (CAD) system in an independent, multicenter dataset. MATERIALS AND METHODS Diagnostic and screening tomosynthesis mammographic examinations (n = 175; cranial caudal and mediolateral oblique) were randomly selected from a previous institutional review board-approved trial. All subjects gave informed consent. Examinations were performed in three centers and included 123 patients, with 132 biopsy-proven screening-detected cancers, and 52 examinations with negative results at 1-year follow-up. One hundred eleven lesions were masses and/or microcalcifications (72 masses, 22 microcalcifications, 17 masses with microcalcifications) and 21 were architectural distortions. Lesions were annotated by radiologists who were aware of all available reports. CAD performance was assessed as per-lesion sensitivity and false-positive results per volume in patients with negative results. RESULTS Use of the CAD system showed per-lesion sensitivity of 89% (99 of 111; 95% confidence interval: 81%, 94%), with 2.7 ± 1.8 false-positive rate per view, 62 of 72 lesions detected were masses, 20 of 22 were microcalcification clusters, and 17 of 17 were masses with microcalcifications. Overall, 37 of 39 microcalcification clusters (95% sensitivity, 95% confidence interval: 81%, 99%) and 79 of 89 masses (89% sensitivity, 95% confidence interval: 80%, 94%) were detected with the CAD system. On average, 0.5 false-positive rate per view were microcalcification clusters, 2.1 were masses, and 0.1 were masses and microcalcifications. CONCLUSION A digital breast tomosynthesis CAD system can allow detection of a large percentage (89%, 99 of 111) of breast cancers manifesting as masses and microcalcification clusters, with an acceptable false-positive rate (2.7 per breast view). Further studies with larger datasets acquired with equipment from multiple vendors are needed to replicate the findings and to study the interaction of radiologists and CAD systems.

Breast MRI Using a High-Relaxivity Contrast Agent: An Overview

OBJECTIVE The purpose of this article is to review the use of gadobenate dimeglumine, a high-relaxivity gadolinium-based contrast material, for breast MRI. CONCLUSION Thanks to its high relaxivity, gadobenate dimeglumine offers valuable advantages in terms of lesion conspicuity, detection rate, and sensitivity for malignant breast lesions. However, a higher enhancement of benign lesions should be taken into account to avoid reduced specificity.