Bilateral gradient-echo spectroscopic imaging with correction of frequency variations for measurement of fatty acid composition in mammary adipose tissue.

PURPOSE: To develop a simultaneous dual-slab three-dimensional gradient-echo spectroscopic imaging (GSI) technique with frequency drift compensation for rapid (<6 min) bilateral measurement of fatty acid composition (FAC) in mammary adipose tissue. METHODS: A bilateral GSI sequence was developed using a simultaneous dual-slab excitation followed by 128 monopolar echoes. A short train of navigator echoes without phase or partition encoding was included at the beginning of each pulse repetition time period to correct for frequency variation caused by respiration and heating of the cryostat. Voxel-wise spectral fitting was applied to measure the areas of the lipid spectral peaks to estimate the number of double-bond (ndb), number of methylene-interrupted double-bond (nmidb), and chain length (cl). The proposed method was tested in an oil phantom and 10 postmenopausal women to assess the influence of the frequency variation on FAC estimation. RESULTS: The frequency drift observed over 5:27 min during the phantom scan was about 10 Hz. Phase correction based on the navigator reduced the median error of ndb, nmidb, and cl from 9.7%, 17.6%, and 3.2% to 2.1%, 9.5%, and 2.8%, respectively. The in vivo data showed a mean ± standard deviation frequency drift of 17.4 ± 2.5 Hz, with ripples at 0.3 ± 0.1 Hz. Our reconstruction algorithm successfully separated signals from the left and right breasts with negligible residual aliasing. Phase correction reduced the interquartile range within each subject's adipose tissue of ndb, nmidb, and cl by 18.4 ± 10.6%, 18.5 ± 13.9%, and 18.4 ± 10.6%, respectively. CONCLUSION: This study shows the feasibility of obtaining bilateral spectroscopic imaging data in the breast and that incorporation of a frequency navigator improves the estimation of FAC.

Comparison between qualitative and quantitative assessment of background parenchymal enhancement on breast MRI.

BACKGROUND: Potential clinical implications of the level of background parenchymal enhancement (BPE) on breast MRI are increasing. Currently, BPE is typically evaluated subjectively. Tests of concordance between subjective BPE assessment and computer-assisted quantified BPE have not been reported. PURPOSE OR HYPOTHESIS: To compare subjective radiologist assessment of BPE with objective quantified parenchymal enhancement (QPE). STUDY TYPE: Cross-sectional observational study. POPULATION: Between 7/24/2015 and 11/27/2015, 104 sequential patients (ages 23 - 81 years, mean 49 years) without breast cancer underwent breast MRI and were included in this study. FIELD STRENGTH/SEQUENCE: 3T; fat suppressed axial T2, axial T1, and axial fat suppressed T1 before and after intravenous contrast. ASSESSMENT: Four breast imagers graded BPE at 90 and 180 s after contrast injection on a 4-point scale (a-d). Fibroglandular tissue masks were generated using a phantom-validated segmentation algorithm, and were co-registered to pre- and postcontrast fat suppressed images to define the region of interest. QPE was calculated. STATISTICAL TESTS: Receiver operating characteristic (ROC) analyses and kappa coefficients (k) were used to compare subjective BPE with QPE. RESULTS: ROC analyses indicated that subjective BPE at 90 s was best predicted by quantified QPE ≤20.2 = a, 20.3-25.2 = b, 25.3-50.0 = c, >50.0 = d, and at 180 s by quantified QPE ≤ 32.2 = a, 32.3-38.3 = b, 38.4-74.5 = c, >74.5 = d. Agreement between subjective BPE and QPE was slight to fair at 90 s (k = 0.20-0.36) and 180 s (k = 0.19-0.28). At higher levels of QPE, agreement between subjective BPE and QPE significantly decreased for all four radiologists at 90 s (P ≤ 0.004) and for three of four radiologists at 180 s (P ≤ 0.004). DATA CONCLUSION: Radiologists were less consistent with QPE as QPE increased. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1685-1691.

Evaluation of Breast Lipid Composition in Patients with Benign Tissue and Cancer by Using Multiple Gradient-Echo MR Imaging.

Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three-dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 ± 0.06 vs 0.46 ± 0.10; P < .05) and SFA was higher (0.31 ± 0.07 vs 0.19 ± 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 ± 0.06 vs 0.27 ± 0.05; P < .01) and lower SFA (0.19 ± 0.11 vs 0.30 ± 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. (©) RSNA, 2016 Online supplemental material is available for this article.

Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

PURPOSE: To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. MATERIALS AND METHODS: This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. RESULTS: The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. CONCLUSION: Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. KEY POINTS: • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

Comparison of fitting methods and b-value sampling strategies for intravoxel incoherent motion in breast cancer.

PURPOSE: To compare fitting methods and sampling strategies, including the implementation of an optimized b-value selection for improved estimation of intravoxel incoherent motion (IVIM) parameters in breast cancer. METHODS: Fourteen patients (age, 48.4 ± 14.27 years) with cancerous lesions underwent 3 Tesla breast MRI examination for a HIPAA-compliant, institutional review board approved diffusion MR study. IVIM biomarkers were calculated using "free" versus "segmented" fitting for conventional or optimized (repetitions of key b-values) b-value selection. Monte Carlo simulations were performed over a range of IVIM parameters to evaluate methods of analysis. Relative bias values, relative error, and coefficients of variation (CV) were obtained for assessment of methods. Statistical paired t-tests were used for comparison of experimental mean values and errors from each fitting and sampling method. RESULTS: Comparison of the different analysis/sampling methods in simulations and experiments showed that the "segmented" analysis and the optimized method have higher precision and accuracy, in general, compared with "free" fitting of conventional sampling when considering all parameters. Regarding relative bias, IVIM parameters fp and Dt differed significantly between "segmented" and "free" fitting methods. CONCLUSION: IVIM analysis may improve using optimized selection and "segmented" analysis, potentially enabling better differentiation of breast cancer subtypes and monitoring of treatment.

Evaluation of the kinetic properties of background parenchymal enhancement throughout the phases of the menstrual cycle.

PURPOSE: To develop and apply a semiautomatic method of segmenting fibroglandular tissue to quantify magnetic resonance (MR) imaging contrast material-enhancement kinetics of breast background parenchyma (BP) and lesions throughout the phases of the menstrual cycle in women with benign and malignant lesions. MATERIALS AND METHODS: The institutional review board approved this retrospective HIPAA-compliant study, and informed consent was waived. From December 2008 to August 2011, 58 premenopausal women who had undergone contrast material-enhanced MR imaging and MR imaging-guided biopsy were identified. The longest time from the start of the last known period was 34 days. One lesion per patient (37 benign and 21 malignant) was analyzed. The patient groups were stratified according to the week of the menstrual cycle when MR imaging was performed. A method based on principal component analysis (PCA) was applied for quantitative analysis of signal enhancement in the BP and lesions by using the percentage of slope and percentage of enhancement. Linear regression and the Mann-Whitney U test were used to assess the association between the kinetic parameters and the week of the menstrual cycle. RESULTS: In the women with benign lesions, percentages of slope and enhancement for both BP and lesions during week 2 were significantly (P < .05) lower than those in week 4. Percentage of enhancement in the lesion in week 2 was lower than that in week 3 (P < .05). The MR images of women with malignant lesions showed no significant difference between the weeks for any of the parameters. There was a strong positive correlation between lesion and BP percentage of slope (r = 0.72) and between lesion and BP percentage of enhancement (r = 0.67) in the benign group. There was also a significant (P = .03) difference in lesion percentage of slope between the benign and malignant groups at week 2. CONCLUSION: The PCA-based method can quantify contrast enhancement kinetics of BP semiautomatically, and kinetics of BP and lesions vary according to the week of the menstrual cycle in benign but not in malignant lesions.

Differentiation of malignant and benign breast lesions using magnetization transfer imaging and dynamic contrast-enhanced MRI.

PURPOSE: To evaluate feasibility of using magnetization transfer ratio (MTR) in conjunction with dynamic contrast-enhanced MRI (DCE-MRI) for differentiation of benign and malignant breast lesions at 3 Tesla. MATERIALS AND METHODS: This prospective study was IRB and HIPAA compliant. DCE-MRI scans followed by MT imaging were performed on 41 patients. Regions of interest (ROIs) were drawn on co-registered MTR and DCE postcontrast images for breast structures, including benign lesions (BL) and malignant lesions (ML). Initial enhancement ratio (IER) and delayed enhancement ratio (DER) were calculated, as were normalized MTR, DER, and IER (NMTR, NDER, NIER) values. Diagnostic accuracy analysis was performed. RESULTS: Mean MTR in ML was lower than in BL (P < 0.05); mean DER and mean IER in ML were significantly higher than in BL (P < 0.01, P < 0.001). NMTR, NDER, and NIER were significantly lower in ML versus BL (P < 0.007, P < 0.001, P < 0.001). IER had highest diagnostic accuracy (77.6%), sensitivity (86.2%), and area under the ROC curve (.879). MTR specificity was 100%. Logistic regression modeling with NMTR and NIER yielded best results for BL versus ML (sensitivity 93.1%, specificity 80%, AUC 0.884, accuracy 83.7%). CONCLUSION: Isolated quantitative DCE analysis may increase specificity of breast MR for differentiating BL and ML. DCE-MRI with NMTR may produce a robust means of evaluating breast lesions.

Dynamic Contrast-Enhanced MRI Evaluation of Pathologic Complete Response in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer After HER2-Targeted Therapy.

RATIONALE AND OBJECTIVES: Pathologic complete response (pCR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after HER2-targeted therapy correlates increased disease-free survival and decreased mastectomy rates. The aim of this study was to explore tumor shrinkage patterns and initial tumor enhancement with pCR in HER2-positive breast cancer. MATERIALS AND METHODS: This was an institutional review board-approved retrospective analysis of 51 HER2 positive breast cancer patients with breast MRI both pre- and post-HER2-targeted therapy. Initial enhancement ratio (IER, initial enhancement percentage over baseline at first postcontrast imaging), pattern of tumor shrinkage, and Dynamic contrast enhanced (DCE)-MRI imaging features were assessed. Wilcoxon rank, Spearman correlation, Fisher's exact, and Mann-Whitney tests were used to correlate MRI imaging features with pCR. IER reader agreement was evaluated by intraclass correlation. Binary logistic regression was used to evaluate multivariate associations with pCR. RESULTS: 56.9% (29/51) of patients had pCR at surgery. Concentric tumor shrinkage pattern was associated with pCR (p = 0.001, Area under the curve (AUC) 0.778): accuracy 80.4%, specificity 96.6%, and sensitivity of 59.1%. There was no association with pCR and imaging response as defined by RECIST criteria (p = 0.169), pretreatment IER (Reader 1 (R1) p = 0.665, Reader 2 (R2) p = 0.766), or lesion size (p = 0.69). IER was associated with axillary metastases (R1 p = 0.016, R2 < 0.001) and ki-67 (R1 r = 0.52, p = 0.008, R2 r = -0.44, p = 0.028). CONCLUSION: The shrinkage pattern of HER2-positive tumors after targeted therapy may be associated with pCR. There was no association between IER and pCR. Future studies evaluating the correlation of shrinkage patterns to texture radiomics are of interest.

Fatty acid composition in mammary adipose tissue measured by Gradient-echo Spectroscopic MRI and its association with breast cancers.

PURPOSE: To assess the association of fatty acid levels in mammary adipose tissue of postmenopausal women with the presence of breast cancer using the Gradient-echo Spectroscopic Imaging (GSI). MATERIALS AND METHODS: Unilateral GSI was performed at 3 T in 61 postmenopausal women undergoing breast MRI exams. The study included 19 women with breast cancer, 23 women with benign/high risk lesions, and 19 women with a history of cancer. Voxel-wise spectral analysis of fatty acids was conducted to measure relative portions of monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fatty acids (SFA) in each voxel. The voxels within mammary adipose tissue were automatically selected and their median fatty acid fractions were used for quantitative analysis. Statistical analyses were performed using χ2 test, one-way analysis of variance (ANOVA) with Tukey-Kramer multiple comparison tests, and linear regression. RESULTS: Postmenopausal women with malignancies had significantly higher SFA (0.336 ± 0.038) in mammary adipose tissue compared to those with benign disease (0.283 ± 0.046, p = 0.0008) and to those with a history of breast cancer (0.287 ± 0.050, p = 0.0038). Postmenopausal women with malignant lesions had significantly lower MUFA (0.352 ± 0.041) compared to those with benign disease (0.401 ± 0.043, p = 0.0032) and with history of breast cancer (0.388 ± 0.055, p = 0.0484). The history of cancer group had a significant correlation (r = 0.60, p = 0.006) between SFA and BMI, and the cancer group had a significant correlation (r = 0.57, p = 0.010) between PUFA and BMI. CONCLUSIONS: Fatty acid composition of mammary adipose tissue, particularly higher SFA and lower MUFA, may be associated with breast cancer. The GSI method utilizes an automated voxel-based analysis to measure fatty acid composition, and may be used to assess the role of mammary adipose tissue in cancer development and progress.

Comprehensive Dynamic Contrast-Enhanced 3D Magnetic Resonance Imaging of the Breast With Fat/Water Separation and High Spatiotemporal Resolution Using Radial Sampling, Compressed Sensing, and Parallel Imaging.

OBJECTIVES: The aim of this study was to assess the applicability of Dixon radial volumetric encoding (Dixon-RAVE) for comprehensive dynamic contrast-enhanced 3D magnetic resonance imaging (MRI) of the breast using a combination of radial sampling, model-based fat/water separation, compressed sensing, and parallel imaging. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, 24 consecutive patients underwent bilateral breast MRI, including both conventional fat-suppressed and non-fat-suppressed precontrast T1-weighted volumetric interpolated breath-hold examination (VIBE). Afterward, 1 continuous Dixon-RAVE scan was performed with the proposed approach while the contrast agent was injected. This scan was immediately followed by the acquisition of 4 conventional fat-saturated VIBE scans. From the comprehensive Dixon-RAVE data set, different image contrasts were reconstructed that are comparable to the separate conventional VIBE scans.Two radiologists independently rated image quality, conspicuity of fibroglandular tissue from fat (FG), and degree of fat suppression (FS) on a 5-point Likert-type scale for the following 3 comparisons: precontrast fat-suppressed (pre-FS), precontrast non-fat-suppressed (pre-NFS), and dynamic fat-suppressed (dyn-FS) images. RESULTS: When scores were averaged over readers, Dixon-RAVE achieved significantly higher (P < 0.001) degree of fat suppression compared with VIBE, for both pre-FS (4.25 vs 3.67) and dyn-FS (4.10 vs 3.46) images. Although Dixon-RAVE had lower image quality score compared with VIBE for the pre-FS (3.56 vs 3.67, P = 0.490), the pre-NFS (3.54 vs 3.88, P = 0.009), and the dyn-FS images (3.06 vs 3.67, P < 0.001), acceptable or better diagnostic quality was achieved (score ≥ 3). The FG score for Dixon-RAVE in comparison to VIBE was significantly higher for the pre-FS image (4.23 vs 3.85, P = 0.044), lower for the pre-NFS image (3.98 vs 4.25, P = 0.054), and higher for the dynamic fat-suppressed image (3.90 vs 3.85, P = 0.845). CONCLUSIONS: Dixon-RAVE can serve as a one-stop-shop approach for comprehensive T1-weighted breast MRI with diagnostic image quality, high spatiotemporal resolution, reduced overall scan time, and improved fat suppression compared with conventional imaging.

Assessment of Background Parenchymal Enhancement and Lesion Kinetics in Breast MRI of BRCA 1/2 Mutation Carriers Compared to Matched Controls Using Quantitative Kinetic Analysis.

RATIONALE AND OBJECTIVES: To investigate whether quantitative kinetic analysis of lesions and background parenchyma in breast magnetic resonance imaging can elucidate differences between BRCA carriers and sporadic controls with high risk for breast cancer. MATERIALS AND METHODS: Fifty-nine BRCA and 59 control cases (49 benign, 10 malignant) were examined in this study. Principal component analysis was applied for quantitative analysis of dynamic signal in background parenchyma (B) and lesion (L) in terms of initial enhancement ratio (IER) and delayed enhancement ratio (DER). RESULTS: Control B-IER, B-DER, L-IER, and L-DER were higher than BRCA cases in all women and in women with benign lesions; statistically significant differences in B-IER and B-DER (all women: P = 0.02 and P = 0.02, respectively; benign only: P = 0.005 and P = 0.005, respectively). In the control cohort, B-IER and B-DER were higher in the premenopausal women than in the postmenopausal women (P = 0.013 and 0.003, respectively), but not in the BRCA cohort; this led to significant differences in B-IER and B-DER between the control and the BRCA groups in the premenopausal women (P = 0.01 and 0.01, respectively) but not in the postmenopausal women. CONCLUSION: Results suggest possible differences in the vascular properties of background parenchyma between BRCA carriers and noncarriers and its association with menopausal status.