A new algorithm for automatic vascular mapping of DCE-MRI of the breast: Clinical application of a potential new biomarker.

BACKGROUND AND OBJECTIVE: Vascularity evaluation on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a potential diagnostic value, but it represents a time consuming procedure, affected by intra- and inter-observer variability. This study tests the application of a recently published method to reproducibly quantify breast vascularity, and evaluates if the vascular volume of cancer-bearing breast, calculated from automatic vascular maps (AVMs), may correlate with pathologic tumor response after neoadjuvant chemotherapy (NAC). METHODS: Twenty-four patients with unilateral locally advanced breast cancer underwent DCE-MRI before and after NAC, 8 responders and 16 non-responders. A validated algorithm, based on multiscale 3D Hessian matrix analysis, provided AVMs and allowed the calculation of vessel volume before the initiation and after the last NAC cycle for each breast. For cancer bearing breast, the difference in vascular volume before and after NAC was compared in responders and non-responders using the Wilcoxon two-sample test. A radiologist evaluated the vascularity on the subtracted images (first enhanced minus unenhanced), before and after treatment, assigning a vascular score for each breast, according to the number of vessels with length ≥30mm and maximal transverse diameter ≥2mm. The same evaluation was repeated with the support of the simultaneous visualization of the AVMs. The two evaluations were compared in terms of mean number of vessels and mean vascular score per breast, in responders and non-responders, by use of Wilcoxon two sample test. For all the analysis, the statistical significance level was set at 0.05. RESULTS: For breasts harboring the cancer, evidence of a difference in vascular volume before and after NAC for responders (median=1.71cc) and non-responders (median=0.41cc) was found (p=0.003). A significant difference was also found in the number of vessels (p=0.03) and vascular score (p=0.02) before or after NAC, according to the evaluation supported by the AVMs. CONCLUSIONS: The encouraging, although preliminary, results of this study suggest the use of AVMs as new biomarker to evaluate the pathologic response after NAC, but also support their application in other breast DCE-MRI vessel analysis that are waiting for a reliable quantification method.

Contrast-enhanced MR imaging of the breast: association between asymmetric increased breast vascularity and ipsilateral cancer in a consecutive series of 197 patients.

PURPOSE: This study was done to estimate the diagnostic performance of an asymmetric increase in breast vascularity (AIBV) for ipsilateral cancer. MATERIALS AND METHODS: A total of 197 patients without previous breast interventions underwent bilateral contrast-enhanced (gadoterate meglumine, 0.1 mmol/kg) magnetic resonance (MR) imaging. Vessels >-2 mm in diameter and ≥ 3 cm in length were counted on maximum intensity projections: a difference ≥ 2 in number between the two breasts was considered AIBV. Pathology or ≥ 1 year follow-up served as a reference standard. The difference in sensitivity of AIBV between invasive and ductal carcinoma in situ (DCIS) as well as the association between AIBV and the diameter of invasive lesions or the histological grade were evaluated using χ(2) test. RESULTS: Pathology revealed 82 malignancies and 20 benign lesions: 70 invasive carcinomas (57 ductal, nine lobular, three mucinous, one papillary) and 12 DCIS: 10 fibroadenomas, two papillomas, two atypical ductal hyperplasias and six other benign lesions. The remaining 95 patients were negative at follow-up. Sensitivity of AIBV was 74% (61/82), specificity 94% (108/115), accuracy 86% (169/197), positive predictive value 90% (61/68) and negative predictive value 84% (108/129). Sensitivity for invasive cancers (80%; 56/70) was significantly higher than that for DCIS (42%; 5/12) (p<0.001). For invasive cancers, sensitivity was 40% (2/5) for lesions ≤ 9 mm in diameter, 69% (9/13) for those 10-14 mm, 79% (15/19) for those 15-19 mm and 91% (30/33) for those ≥ 20 mm (p<0.001). The G3 lesion rate was 49% (27/55) among true positives and only 7% (1/14) among false negatives (p=0.009). CONCLUSIONS: An association between AIBV and ipsilateral cancer exists, particularly for invasive cancers ≥ 20 mm or with high pathologic grade.

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.

Contrast-enhanced breast MR imaging of claustrophobic or oversized patients using an open low-field magnet.

PURPOSE: A number of women who should undergo magnetic resonance (MR) imaging of the breast cannot use this diagnostic tool due to claustrophobia or excessive body size for the restricted confines of standard closed MR systems. Our aim was to evaluate the performance of open low-field magnet breast MR imaging in such patients using a high-relaxivity contrast agent. MATERIALS AND METHODS: Of 397 consecutive patients undergoing breast MR imaging, 379 (95.5%) were studied at 1.5 T. Due to claustrophobia (n=15) or large body size (n=3), 18 patients (4.5%) were studied on a 0.2-T open magnet using a body coil. A 3D dynamic T1-weighted gradient-echo 94-s sequence was acquired with intravenous injection of gadobenate dimeglumine (0.1 mmol/kg). The standard of reference was pathological examination for 16 lesions classified with a maximal Breast Imaging Reporting and Data System (BI-RADS) score from 3 to 5, fine-needle aspiration cytology and >or=2-year follow-up for two lesions classified as BI-RADS 3, and >or=2-years follow-up for five lesions classified as BI-RADS 2. RESULTS: Diagnostic MR image quality was achieved for 20/23 lesions in 15/18 patients. Three lesions (two invasive cancers and a cyst) were not assessed due to patient movement and considered as two false negatives and one false positive. Thus, an 86% sensitivity [13/15; 95% confidence interval (CI): 70%-100%], an 87% specificity (7/8; 95% CI: 65%-100%) and an 87% accuracy (20/23; 95% CI: 73%-100%) were obtained. The intraclass correlation coefficient between MR and pathologic lesion size was 0.845. CONCLUSION: In claustrophobic or oversized patients, open low-field breast MR with gadobenate dimeglumine yields good diagnostic performance.

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.

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 < or =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 standard. RESULTS: 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); > or =5 and <10 mm (n=7); > or =10 and <20 mm (n=3); > or =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 examination. CONCLUSIONS: When the whole breast is used as the histopathological reference standard, both mammography and MRI show low sensitivity for DCIS.

Front-surface absorbance spectra of wheat flour: determination of carotenoids.

Front-surface absorbance spectra of wheat flours in the 250-650 nm region can be obtained by measuring reflectance spectra with a conventional spectrofluorometer suitably set to detect light scattered from powder samples. The spectra recorded on flour samples, obtained from seeds of four bread and five durum wheats, show high-intensity absorption bands due to aromatic amino acids of wheat proteins and low-intensity bands due to chromophores bound to low-molecular-weight compounds. The intensity of these last bands is proportional to the concentration of the corresponding chromophores present in the flour; thus, it can be used to measure the content of the compounds containing the chromophore(s). In particular, a quantitative determination of the carotenoids actually present in the flours is made, obtaining information on the original content of the seeds. This determination is important, as, for example, xanthophylls are well-known antioxidants and free-radical scavengers involved in aging processes of seeds. Reflectance measurements on powder samples are far more economic in terms of time and materials consumption than methods such as extraction and HPLC analysis of extracts and, in addition, give an evaluation of the overall content of carotenoids with absorption bands in the spectral range 450-500 nm. Application of the technique to other food powders with low-intensity absorption bands in the near-UV and vis region is possible.

Mechanism of action of indomethacin in tubular defects.

Indomethacin, a potent prostaglandin synthesis inhibitor, has been proven to be effective in a number of tubular defects characterized by enhanced prostaglandin (namely, prostaglandin E2 (PGE2) production, but its mechanism of action is poorly understood. To elucidate further the mechanism(s) by which indomethacin reverses the abnormal tubular functions, five children with different tubular defects (nephrogenic diabetes insipidus, three cases; Fanconi syndrome, one case; and pseudohypoaldosteronism, one case) were treated with indomethacin. Indomethacin, 1 mg/kg every eight hours, was given for 1 week to all children and then was given chronically to four of the children who responded to the drug. Its use was suspended in a 10 year-old-boy with nephrogenic diabetes insipidus because it proved ineffective. To assess the site along the nephron where indomethacin affects the solute and water excretion, an acute water load study was performed in three responsive children before and during the treatment. Indomethacin did not significantly alter the glomerular filtration rate but was effective in reducing diuresis and levels of urinary sodium and potassium excretion. In the child with Fanconi syndrome, indomethacin was also effective in controlling the urinary loss of phosphate, urate, glucose, and bicarbonate. Results of the water load studies show that indomethacin decreases the delivery of solute from the proximal tubule, reduces the fractional free water clearance, and increases the urine-plasma osmolar ratio.(ABSTRACT TRUNCATED AT 250 WORDS)