Quantitative evaluation of contrast agent uptake in standard fat-suppressed dynamic contrast-enhanced MRI examinations of the breast.

PURPOSE: To propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast-enhanced (DCE) examinations undertaken with standard clinical fat-suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas. METHODS: A standard fat-suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)-weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre-, peak-, and post-contrast agent administration) for 20 patients, pre-treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank-sum test). RESULTS: The calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat-suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre-, peak-, and post-contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post-contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post-contrast T1 values, potentially related to their infiltrative growth pattern. CONCLUSIONS: This work has demonstrated the feasibility of fat-suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.

Ultrasound Tomography Evaluation of Breast Density: A Comparison With Noncontrast Magnetic Resonance Imaging.

OBJECTIVES: Ultrasound tomography (UST) is an emerging whole-breast 3-dimensional imaging technique that obtains quantitative tomograms of speed of sound of the entire breast. The imaged parameter is the speed of sound which is used as a surrogate measure of density at each voxel and holds promise as a method to evaluate breast density without ionizing radiation. This study evaluated the technique of UST and compared whole-breast volume averaged speed of sound (VASS) with MR percent water content from noncontrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Forty-three healthy female volunteers (median age, 40 years; range, 29-59 years) underwent bilateral breast UST and MRI using a 2-point Dixon technique. Reproducibility of VASS was evaluated using Bland-Altman analysis. Volume averaged speed of sound and MR percent water were evaluated and compared using Pearson correlation coefficient. RESULTS: The mean ± standard deviation VASS measurement was 1463 ± 29 m s (range, 1434-1542 m s). There was high similarity between right (1464 ± 30 m s) and left (1462 ± 28 m s) breasts (P = 0.113) (intraclass correlation coefficient, 0.98). Mean MR percent water content was 35.7% ± 14.7% (range, 13.2%-75.3%), with small but significant differences between right and left breasts (36.3% ± 14.9% and 35.1% ± 14.7%, respectively; P = 0.004). There was a very strong correlation between VASS and MR percent water density (r = 0.96, P < 0.0001). CONCLUSIONS: Ultrasound tomography holds promise as a reliable and reproducible 3-dimensional technique to provide a surrogate measure of breast density and correlates strongly with MR percent water content.

Comparison of Dixon Sequences for Estimation of Percent Breast Fibroglandular Tissue.

OBJECTIVES: To evaluate sources of error in the Magnetic Resonance Imaging (MRI) measurement of percent fibroglandular tissue (%FGT) using two-point Dixon sequences for fat-water separation. METHODS: Ten female volunteers (median age: 31 yrs, range: 23-50 yrs) gave informed consent following Research Ethics Committee approval. Each volunteer was scanned twice following repositioning to enable an estimation of measurement repeatability from high-resolution gradient-echo (GRE) proton-density (PD)-weighted Dixon sequences. Differences in measures of %FGT attributable to resolution, T1 weighting and sequence type were assessed by comparison of this Dixon sequence with low-resolution GRE PD-weighted Dixon data, and against gradient-echo (GRE) or spin-echo (SE) based T1-weighted Dixon datasets, respectively. RESULTS: %FGT measurement from high-resolution PD-weighted Dixon sequences had a coefficient of repeatability of ±4.3%. There was no significant difference in %FGT between high-resolution and low-resolution PD-weighted data. Values of %FGT from GRE and SE T1-weighted data were strongly correlated with that derived from PD-weighted data (r = 0.995 and 0.96, respectively). However, both sequences exhibited higher mean %FGT by 2.9% (p < 0.0001) and 12.6% (p < 0.0001), respectively, in comparison with PD-weighted data; the increase in %FGT from the SE T1-weighted sequence was significantly larger at lower breast densities. CONCLUSION: Although measurement of %FGT at low resolution is feasible, T1 weighting and sequence type impact on the accuracy of Dixon-based %FGT measurements; Dixon MRI protocols for %FGT measurement should be carefully considered, particularly for longitudinal or multi-centre studies.

Alternative screening for dense breasts: MRI.

OBJECTIVE. The purpose of this article is to review the use of MRI in breast density measurement and breast cancer risk estimation and to discuss the role of MRI as an alternative screening to mammography for screening women with dense breasts. CONCLUSION. The potential of MRI for screening women with dense breasts remains controversial because of the paucity of clinical evidence, the possibility of overdiagnosis, and the cost-effectiveness of the technique in this population. Although methods of MRI measurement require standardization and automation, future addition of MRI density to risk models may positively impact their value.

Investigating the influence of flip angle and k-space sampling on dynamic contrast-enhanced MRI breast examinations.

RATIONALE AND OBJECTIVES: To retrospectively investigate the effect of flip angle (FA) and k-space sampling on the performance of dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) breast sequences. MATERIALS AND METHODS: Five DCE-MRI breast sequences were evaluated (10°, 14°, and 18° FAs; radial or linear k-space sampling), with 7-10 patients in each group (n = 45). All sequences were compliant with current technical breast screening guidelines. Contrast agent (CA) uptake curves were constructed from the right mammary artery for each examination. Maximum relative enhancement, E(max), and time-to-peak enhancement, T(max), were measured and compared between protocols (analysis of variance and Mann-Whitney). For each sequence, calculated values of maximum relative enhancement, E(calc), were derived from the Bloch equations and compared to E(max). Fat suppression performance (residual bright fat and chemical shift artifact) was rated for each examination and compared between sequences (Fisher exact tests). RESULTS: Significant differences were identified between DCE-MRI sequences. E(max) increased significantly at higher FAs and with linear k-space sampling (P < .0001; P = .001). Radial protocols exhibited greater T(max) than linear protocols at FAs of both 14° (P = .025) and 18° (P < .0001), suggesting artificially flattened uptake curves. Good correlation was observed between E(calc) and E(max) (r = 0.86). Fat suppression failure was more pronounced at an FA of 18° (P = .008). CONCLUSIONS: This retrospective approach is validated as a tool to compare and optimize breast DCE-MRI sequences. Alterations in FA and k-space sampling result in significant differences in CA uptake curve shape which could potentially affect diagnostic interpretation. These results emphasize the need for careful parameter selection and greater standardization of breast DCE-MRI sequences.

Ruthenium-catalyzed meta sulfonation of 2-phenylpyridines.

A selective catalytic meta sulfonation of 2-phenylpyridines was found to occur in the presence of (arene)ruthenium(II) complexes upon reaction with sulfonyl chlorides. The 2-pyridyl group facilitates the formation of a stable Ru-C(aryl) σ bond that induces a strong para-directing effect. Electrophilic aromatic substitution proceeds with the sulfonyl chloride to furnish a sulfone at the position meta to the chelating group. This new catalytic process offers access to atypical regioselectivity for reactions involving chelation-assisted cyclometalation.

Ruthenium bidentate phosphine complexes for the coordination and catalytic dehydrogenation of amine- and phosphine-boranes.

Addition of the amine-boranes H(3)B⋅NH(2)tBu, H(3)B⋅NHMe(2) and H(3)B⋅NH(3) to the cationic ruthenium fragment [Ru(xantphos)(PPh(3))(OH(2))H][BAr(F)(4)] (2; xantphos=4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; BAr(F)(4)=[B{3,5-(CF(3))(2)C(6)H(3)}(4)](-)) affords the η(1)-B-H bound amine-borane complexes [Ru(xantphos)(PPh(3))(H(3)B⋅NH(2)tBu)H][BAr(F)(4)] (5), [Ru(xantphos)(PPh(3))(H(3) B⋅NHMe(2))H][BAr(F)(4)] (6) and [Ru(xantphos)(PPh(3))(H(3)B⋅NH(3))H][BAr(F)(4)] (7). The X-ray crystal structures of 5 and 7 have been determined with [BAr(F)(4)] and [BPh(4)] anions, respectively. Treatment of 2 with H(3)B⋅PHPh(2) resulted in quite different behaviour, with cleavage of the B-P interaction taking place to generate the structurally characterised bis-secondary phosphine complex [Ru(xantphos)(PHPh(2))(2)H][BPh(4)] (9). The xantphos complexes 2, 5 and 9 proved to be poor precursors for the catalytic dehydrogenation of H(3)B⋅NHMe(2). While the dppf species (dppf=1,1'-bis(diphenylphosphino)ferrocene) [Ru(dppf)(PPh(3))HCl] (3) and [Ru(dppf)(η(6)-C(6)H(5)PPh(2))H][BAr(F)(4)] (4) showed better, but still moderate activity, the agostic-stabilised N-heterocyclic carbene derivative [Ru(dppf)(ICy)HCl] (12; ICy=1,3-dicyclohexylimidazol-2-ylidene) proved to be the most efficient catalyst with a turnover number of 76 h(-1) at room temperature.

Pincer phosphine complexes of ruthenium: formation of Ru(P-O-P)(PPh3)HCl (P-O-P = xantphos, DPEphos, (Ph2PCH2CH2)2O) and Ru(dppf)(PPh3)HCl and characterization of cationic dioxygen, dihydrogen, dinitrogen, and arene coordinated phosphine products.

Treatment of Ru(PPh(3))(3)HCl with the pincer phosphines 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (xantphos), bis(2-diphenylphosphinophenyl)ether (DPEphos), or (Ph(2)PCH(2)CH(2))(2)O affords Ru(P-O-P)(PPh(3))HCl (xantphos, 1a; DPEphos, 1b; (Ph(2)PCH(2)CH(2))(2)O, 1c). The X-ray crystal structures of 1a-c show that all three P-O-P ligands coordinate in a tridentate manner through phosphorus and oxygen. Abstraction of the chloride ligand from 1a-c by NaBAr(4)(F) (BAr(4)(F) = B(3,5-C(6)H(3)(CF(3))(2))(4)) gives the cationic aqua complexes [Ru(P-O-P)(PPh(3))(H(2)O)H]BAr(4)(F) (3a-c). Removal of chloride from 1a by AgOTf yields Ru(xantphos)(PPh(3))H(OTf) (2a), which reacts with water to form [Ru(xantphos)(PPh(3))(H(2)O)H](OTf). The aqua complexes 3a-b react with O(2) to generate [Ru(xantphos)(PPh(3))(eta(2)-O(2))H]BAr(4)(F) (5a) and [Ru(DPEphos)(PPh(3))(eta(2)-O(2))H]BAr(4)(F) (5b). Addition of H(2) or N(2) to 3a-c yields the thermally unstable dihydrogen and dinitrogen species [Ru(P-O-P)(PPh(3))(eta(2)-H(2))H]BAr(4)(F) (6a-c) and [Ru(P-O-P)(PPh(3))(N(2))H]BAr(4)(F) (7a-c), which have been characterized by multinuclear NMR spectroscopy at low temperature. Ru(PPh(3))(3)HCl reacts with 1,1'-bis(diphenylphosphino)ferrocene (dppf) to give the 16-electron complex Ru(dppf)(PPh(3))HCl (1d), which upon treatment with NaBAr(4)(F), affords [Ru(dppf){(eta(6)-C(6)H(5))PPh(2)}H]BAr(4)(F) (8), in which the PPh(3) ligand binds eta(6) through one of the PPh(3) phenyl rings. Reaction of 8 with CO or PMe(3) at elevated temperatures yields the 18-electron products [Ru(dppf)(PPh(3))(CO)(2)H]BAr(F)(4) (9) and [Ru(PMe(3))(5)H]BAr(4)(F) (10).

Ruthenium xantphos complexes in hydrogen transfer processes: reactivity and mechanistic studies.

The in situ combination of [Ru(PPh3)3(CO)H2] with xantphos is catalytically active for the alkylation of alcohols with the ketonitrile (t)BuC(O)CH2CN in a model oxidation-Knoevenagel-reduction process. The precursor complex [Ru(xantphos)(PPh3)(CO)H2] was isolated and reacted with stoichiometric amounts of PhCH2OH and PhCHO. Under these conditions, the alcohol is decarbonylated to afford [Ru(xantphos)(CO)2H2] and finally [Ru(xantphos)(CO)3], both of which prove to be less active for catalysis than the starting complex. The reactivity of the xantphos system contrasts with that of [Ru(dppp)(PPh3)(CO)H2], which is catalytically inactive for the Knoevenagel reaction and fails to show any stoichiometric reactivity with alcohols.

[Ru(NHC)(xantphos)(CO)H(2)] complexes: intramolecular C-H activation and applications in C-C bond formation.

Treatment of [Ru(PPh3)(xantphos)(CO)H2] (1) with the N-heterocyclic carbenes (NHCs) IEt2Me2 (1,3-diethyl-4,5-dimethylimidazol-2-ylidene), IiPr2Me2 (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) and IMes (1,3-dimesitylimidazol-2-ylidene) at elevated temperature affords the C-H activated carbene complexes [Ru(NHC)(xantphos)(CO)H] (2-4). In contrast, ICy (1,3-dicyclohexylimidazol-2-ylidene) reacts with 1 to give the substitution product [Ru(ICy)(xantphos)(CO)H2] (6), which can be converted into the C-H activated species [Ru(ICy)(xantphos)(CO)H] (7) upon thermolysis in the presence of H2CCHSiMe3. Addition of H2 to 2 yields [Ru(IEt2Me2)(xantphos)(CO)H2] (5), while H2 reacts with 7 to reform 6. Complexes 2-4 and 7 catalyse the Knoevenagel reaction of PhCH2OH with tBuC(O)CH2CN, although they prove to be somewhat less active than the phosphine complex 1.