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Radiomic signatures with contrast-enhanced magnetic resonance imaging for the assessment of breast cancer receptor status and molecular subtypes: initial results
Leithner, Doris; Horvat, Joao V; Marino, Maria Adele; Bernard-Davila, Blanca; Jochelson, Maxine S; Ochoa-Albiztegui, R Elena; Martinez, Danny F; Morris, Elizabeth A; Thakur, Sunitha; Pinker, Katja
BACKGROUND:To evaluate the diagnostic performance of radiomic signatures extracted from contrast-enhanced magnetic resonance imaging (CE-MRI) for the assessment of breast cancer receptor status and molecular subtypes. METHODS:One hundred and forty-three patients with biopsy-proven breast cancer who underwent CE-MRI at 3 T were included in this IRB-approved HIPAA-compliant retrospective study. The training dataset comprised 91 patients (luminal A, n = 49; luminal B, n = 8; HER2-enriched, n = 11; triple negative, n = 23), while the validation dataset comprised 52 patients from a second institution (luminal A, n = 17; luminal B, n = 17; triple negative, n = 18). Radiomic analysis of manually segmented tumors included calculation of features derived from the first-order histogram (HIS), co-occurrence matrix (COM), run-length matrix (RLM), absolute gradient (GRA), autoregressive model (ARM), discrete Haar wavelet transform (WAV), and lesion geometry (GEO). Fisher, probability of error and average correlation (POE + ACC), and mutual information coefficients were used for feature selection. Linear discriminant analysis followed by k-nearest neighbor classification (with leave-one-out cross-validation) was used for pairwise radiomic-based separation of receptor status and molecular subtypes. Histopathology served as the standard of reference. RESULTS:In the training dataset, radiomic signatures yielded the following accuracies > 80%: luminal B vs. luminal A, 84.2% (mainly based on COM features); luminal B vs. triple negative, 83.9% (mainly based on GEO features); luminal B vs. all others, 89% (mainly based on COM features); and HER2-enriched vs. all others, 81.3% (mainly based on COM features). Radiomic signatures were successfully validated in the separate validation dataset for luminal A vs. luminal B (79.4%) and luminal B vs. triple negative (77.1%). CONCLUSIONS:In this preliminary study, radiomic signatures with CE-MRI enable the assessment of breast cancer receptor status and molecular subtypes with high diagnostic accuracy. These results need to be confirmed in future larger studies.
PMCID:6739929
PMID: 31514736
ISSN: 1465-542x
CID: 5475702
MRI evaluation of axillary and intramammary lymph nodes in the postoperative period
Horvat, Joao V; Morris, Elizabeth A; Bernard-Davila, Blanca; Martinez, Danny F; Leithner, Doris; Ochoa-Albiztegui, Rosa Elena; Thakur, Sunitha B; Pinker, Katja
Our study aimed to evaluate if breast-conserving surgery and adjuvant treatment could affect the morphological features of axillary and intramammary lymph nodes on magnetic resonance imaging (MRI) in patients with invasive breast cancer and clinically negative axilla. In this single-center study, we retrospectively evaluated 50 patients who had (a) breast-conserving surgery, (b) clinically negative axilla, (c) preoperative MRI within 3 months before surgery, and (d) postoperative MRI within 12 months after surgery. Axillary and intramammary lymph nodes on postoperative MRI were identified and then compared with preoperative MRI by two breast radiologists with regards to the following: enlargement, cortical thickening, presence of fatty hilum, irregularity, heterogeneity, matting, and axillary lymph node asymmetry. Three hundred and two axillary and eight intramammary lymph nodes were evaluated. Enlargement and cortical thickening were seen in 5/50 (10%) patients in three axillary and two intramammary lymph nodes. None of the lymph nodes on postoperative MRI demonstrated occurrence of lack of fatty hilum, irregularity, heterogeneity, matting or axillary lymph node asymmetry. No evidence of recurrence was observed on 2-year follow-up. Lymph node enlargement and cortical thickening may be observed in a few patients in the postoperative period. Nevertheless, in patients with clinically negative axilla, these changes in morphology are often related to treatment rather than malignancy and favor short-term follow-up as an alternative to lymph node biopsy.
PMCID:6754287
PMID: 31175688
ISSN: 1524-4741
CID: 5475642
Diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping as a quantitative imaging biomarker for prediction of immunohistochemical receptor status, proliferation rate, and molecular subtypes of breast cancer
Horvat, Joao V; Bernard-Davila, Blanca; Helbich, Thomas H; Zhang, Michelle; Morris, Elizabeth A; Thakur, Sunitha B; Ochoa-Albiztegui, R Elena; Leithner, Doris; Marino, Maria A; Baltzer, Pascal A; Clauser, Paola; Kapetas, Panagiotis; Bago-Horvath, Zsuzsanna; Pinker, Katja
BACKGROUND:Diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping is one of the most useful additional MRI parameters to improve diagnostic accuracy and is now often used in a multiparameric imaging setting for breast tumor detection and characterization. PURPOSE:To evaluate whether different ADC metrics can also be used for prediction of receptor status, proliferation rate, and molecular subtype in invasive breast cancer. STUDY TYPE:Retrospective. SUBJECTS:In all, 107 patients with invasive breast cancer met the inclusion criteria (mean age 57 years, range 32-87) and underwent multiparametric breast MRI. FIELD STRENGTH/SEQUENCE:-weighted turbo-spin echo (TSE) with fatsat. ASSESSMENT:Two readers independently drew a region of interest on ADC maps on the whole tumor (WTu), and on its darkest part (DpTu). Minimum, mean, and maximum ADC values of both WTu and DpTu were compared for receptor status, proliferation rate, and molecular subtypes. STATISTICAL TESTS:Wilcoxon rank sum, Mann-Whitney U-tests for associations between radiologic features and histopathology; histogram and q-q plots, Shapiro-Wilk's test to assess normality, concordance correlation coefficient for precision and accuracy; receiver operating characteristics curve analysis. RESULTS:Estrogen receptor (ER) and progesterone receptor (PR) status had significantly different ADC values for both readers. Maximum WTu (P = 0.0004 and 0.0005) and mean WTu (P = 0.0101 and 0.0136) were significantly lower for ER-positive tumors, while PR-positive tumors had significantly lower maximum WTu values (P = 0.0089 and 0.0047). Maximum WTu ADC was the only metric that was significantly different for molecular subtypes for both readers (P = 0.0100 and 0.0132) and enabled differentiation of luminal tumors from nonluminal (P = 0.0068 and 0.0069) with an area under the curve of 0.685 for both readers. DATA CONCLUSION:Maximum WTu ADC values may be used to differentiate luminal from other molecular subtypes of breast cancer. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:836-846.
PMCID:6767396
PMID: 30811717
ISSN: 1522-2586
CID: 5475622
A multiparametric [18F]FDG PET/MRI diagnostic model including imaging biomarkers of the tumor and contralateral healthy breast tissue aids breast cancer diagnosis
Leithner, Doris; Horvat, Joao V; Bernard-Davila, Blanca; Helbich, Thomas H; Ochoa-Albiztegui, R Elena; Martinez, Danny F; Zhang, Michelle; Thakur, Sunitha B; Wengert, Georg J; Staudenherz, Anton; Jochelson, Maxine S; Morris, Elizabeth A; Baltzer, Pascal A T; Clauser, Paola; Kapetas, Panagiotis; Pinker, Katja
PURPOSE/OBJECTIVE:F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) model for breast cancer diagnosis incorporating imaging biomarkers of breast tumors and contralateral healthy breast tissue. METHODS:F]FDG-PET; and for the contralateral healthy breast, background parenchymal enhancement (BPE) and amount of fibroglandular tissue (FGT) on DCE-MRI, ADCmean on DWI, and SUVmax. Histopathology served as standard of reference. Uni-, bi-, and multivariate logistic regression analyses were performed to assess the relationships between malignancy and imaging features. Predictive discrimination of benign and malignant breast lesions was examined using area under the receiver operating characteristic curve (AUC). RESULTS:There were 100 malignant and 41 benign lesions (size: median 1.9, range 0.5-10 cm). The multivariate regression model incorporating significant univariate predictors identified tumor enhancement kinetics (P = 0.0003), tumor ADCmean (P < 0.001), and BPE of the contralateral healthy breast (P = 0.0019) as independent predictors for breast cancer diagnosis. Other biomarkers did not reach significance. Combination of the three significant biomarkers achieved an AUC value of 0.98 for breast cancer diagnosis. CONCLUSION/CONCLUSIONS:F]FDG PET/MRI diagnostic model incorporating both qualitative and quantitative parameters of the tumor and the healthy contralateral tissue aids breast cancer diagnosis.
PMCID:6647078
PMID: 31197455
ISSN: 1619-7089
CID: 5475652
Quantitative in vivo proton MR spectroscopic assessment of lipid metabolism: Value for breast cancer diagnosis and prognosis
Thakur, Sunitha B; Horvat, Joao V; Hancu, Ileana; Sutton, Olivia M; Bernard-Davila, Blanca; Weber, Michael; Oh, Jung Hun; Marino, Maria Adele; Avendano, Daly; Leithner, Doris; Brennan, Sandra; Giri, Dilip; Manderski, Elizabeth; Morris, Elizabeth A; Pinker, Katja
BACKGROUND:H-MRS) has been largely based on choline metabolites; however, other relevant metabolites can be detected and monitored. PURPOSE:H-MRS can be used for the noninvasive differentiation of benign and malignant breast tumors, differentiation among molecular breast cancer subtypes, and prediction of long-term survival outcomes. STUDY TYPE:Retrospective. SUBJECTS:In all, 168 women, aged ≥18 years. FIELD STRENGTH/SEQUENCE:H-MRS: PRESS with TR/TE = 2000/135 msec, water suppression, and 128 scan averages, in addition to 16 reference scans without water suppression. ASSESSMENT:MRS quantitative analysis of lipid resonances using the LCModel was performed. Histopathology was the reference standard. STATISTICAL TESTS:Categorical data were described using absolute numbers and percentages. For metric data, means (plus 95% confidence interval [CI]) and standard deviations as well as median, minimum, and maximum were calculated. Due to skewed data, the latter were more adequate; unpaired Mann-Whitney U-tests were performed to compare groups without and with Bonferroni correction. ROC analyses were also performed. RESULTS:. Six lipid metabolite peaks were quantified: L09, L13 + L16, L21 + L23, L28, L41 + L43, and L52 + L53. Malignant lesions showed lower L09, L21 + L23, and L52 + L53 than benign lesions (P = 0.022, 0.027, and 0.0006). Similar results were observed for Luminal A or Luminal A/B vs. other molecular subtypes. At follow-up, patients were split into two groups based on median values for the six peaks; recurrence-free survival was significantly different between groups for L09, L21 + L23, and L28 (P = 0.0173, 0.0024, and 0.0045). DATA CONCLUSION:H-MRS assessment of lipid metabolism may provide an additional noninvasive imaging biomarker to guide therapeutic decisions in breast cancer. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:239-249.
PMCID:6579700
PMID: 30605266
ISSN: 1522-2586
CID: 5475602
Abbreviated MRI of the Breast: Does It Provide Value?
Leithner, Doris; Moy, Linda; Morris, Elizabeth A; Marino, Maria A; Helbich, Thomas H; Pinker, Katja
MRI of the breast is the most sensitive test for breast cancer detection and outperforms conventional imaging with mammography, digital breast tomosynthesis, or ultrasound. However, the long scan time and relatively high costs limit its widespread use. Hence, it is currently only routinely implemented in the screening of women at an increased risk of breast cancer. To overcome these limitations, abbreviated dynamic contrast-enhanced (DCE)-MRI protocols have been introduced that substantially shorten image acquisition and interpretation time while maintaining a high diagnostic accuracy. Efforts to develop abbreviated MRI protocols reflect the increasing scrutiny of the disproportionate contribution of radiology to the rising overall healthcare expenditures. Healthcare policy makers are now focusing on curbing the use of advanced imaging examinations such as MRI while continuing to promote the quality and appropriateness of imaging. An important cornerstone of value-based healthcare defines value as the patient's outcome over costs. Therefore, the concept of a fast, abbreviated MRI exam is very appealing, given its high diagnostic accuracy coupled with the possibility of a marked reduction in the cost of an MRI examination. Given recent concerns about gadolinium-based contrast agents, unenhanced MRI techniques such as diffusion-weighted imaging (DWI) are also being investigated for breast cancer diagnosis. Although further larger prospective studies, standardized imaging protocol, and reproducibility studies are necessary, initial results with abbreviated MRI protocols suggest that it seems feasible to offer screening breast DCE-MRI to a broader population. This article aims to give an overview of abbreviated and fast breast MRI protocols, their utility for breast cancer detection, and their emerging role in the new value-based healthcare paradigm that has replaced the fee-for-service model.
PMID: 30194749
ISSN: 1522-2586
CID: 3274892
Gadolinium-enhanced imaging of pediatric thoracic lymphoma: is intravenous contrast really necessary?
Arendt, Christophe T; Beeres, Martin; Leithner, Doris; Tischendorf, Patricia; Langenbach, Marcel; Kaltenbach, Benjamin; Dalgicdir, Jasmin; Vogl, Thomas J; Gruber-Rouh, Tatjana
OBJECTIVES/OBJECTIVE:Increasing awareness of potential side effects from gadolinium-based contrast agents has underlined the need for contrast-free magnetic resonance imaging (MRI). Numerous recent articles evaluated the risk of potential brain deposits, with the result that research is putting the focus more on alternative unenhanced imaging techniques. The aim of this study was to determine the need for contrast media for chest MRI in primary staging and follow-up care of lymphoma. METHODS:This monocentric, retrospective study encompassed patients under 25 years of age who had undergone histopathological examination of thoracic lymph nodes and at least one chest MRI examination with unenhanced and contrast-enhanced sequences. Seven different thoracic lymph node stations including mediastinal, hilar, periclavicular, and axillary regions were evaluated by two readers regarding lesion diameter, number, shape, necrosis, and infiltration of surrounding structures. Findings were categorized into suspicious (> 1 cm; round; necrosis; infiltration) or non-suspicious. RESULTS:Fifty-one patients (mean age, 16.0 ± 3.7 yrs) with thoracic Hodgkin (70.6%) and non-Hodgkin lymphoma (25.5%) and lymphadenopathy (3.9%) were retrospectively included. Most lymph nodes categorized as suspicious were located in the mediastinal station (86.4%). High agreement (κ = 0.81) between unenhanced and contrast-enhanced sequences was found for both suspicious and non-suspicious lymph nodes. Significant (p < 0.001), but small difference (1 mm) was observed only in sizing mediastinal lymph nodes (all other p > 0.05). No significant difference (smallest p = 0.08) was shown for the use of five different types of contrast media. CONCLUSION/CONCLUSIONS:MRI in young patients with thoracic lymphoma can safely be done without the use of contrast agent. KEY POINT/CONCLUSIONS:• Thoracic magnetic resonance imaging in young lymphoma patients can safely be done without gadolinium-based contrast agents.
PMID: 30547199
ISSN: 1432-1084
CID: 5475592
Comparison of Radiation Dose and Image Quality of Contrast-Enhanced Dual-Source CT of the Chest: Single-Versus Dual-Energy and Second-Versus Third-Generation Technology
Lenga, Lukas; Leithner, Doris; Peterke, Julia L; Albrecht, Moritz H; Gudauskas, Tomas; D'Angelo, Tommaso; Booz, Christian; Hammerstingl, Renate; Vogl, Thomas J; Martin, Simon S; Wichmann, Julian L
OBJECTIVE:The purpose of this study was to compare radiation dose and image quality of single- and dual-energy CT (SECT, DECT) examinations of the chest in matched cohorts for second and third-generation dual-source CT (DSCT) systems. MATERIALS AND METHODS:We analyzed 200 patients (100 men; mean age, 61.7 ± 14.8 years old; 100 women, mean age, 59.4 ± 15.1 years old), matched by sex and body mass index, who had undergone clinically indicated contrast-enhanced chest CT. Four study groups, each consisting of 50 patients, were evaluated. Contrast-enhanced chest CT was performed using vendor-preset second-generation DSCT (group A, 120-kV SECT; group C, 80/Sn140-kV DECT) or third-generation DSCT (group B, 90-kV SECT; group D, 90/Sn150-kV DECT) protocols. Radiation dose assessment was normalized to a scan range of 27.5 cm. Image quality was objectively analyzed using dose-independent figure-of-merit (FOM) contrast-to-noise ratio (CNR) calculations and subjectively evaluated by three independent radiologists. RESULTS:Direct comparison of effective radiation dose for second-generation DSCT groups A and C showed statistically significant lower radiation dose values for DECT compared with SECT acquisition (3.2 ± 1.2 mSv vs 2.3 ± 0.6 mSv, p ≤ 0.004), but differences between third-generation SECT and DECT were not significant (1.2 ± 0.9 mSv vs 1.3 ± 0.6 mSv, p = 0.412). FOM CNR analysis revealed highest values for third-generation DECT (p ≤ 0.043). Differences in subjective image quality between the four groups were not statistically significant (p ≥ 0.179). CONCLUSION:Contrast-enhanced DECT examinations of the chest can be performed routinely with second- and third-generation DSCT systems without either increased radiation exposure or decreased image quality compared with SECT acquisition.
PMID: 30699006
ISSN: 1546-3141
CID: 5475612
Multiparametric MRI model with dynamic contrast-enhanced and diffusion-weighted imaging enables breast cancer diagnosis with high accuracy
Zhang, Michelle; Horvat, Joao V; Bernard-Davila, Blanca; Marino, Maria Adele; Leithner, Doris; Ochoa-Albiztegui, R Elena; Helbich, Thomas H; Morris, Elizabeth A; Thakur, Sunitha; Pinker, Katja
BACKGROUND:-weighted imaging are most strongly associated with a breast cancer diagnosis. PURPOSE/HYPOTHESIS:-weighted imaging, and DWI with apparent diffusion coefficient (ADC) mapping. STUDY TYPE:Retrospective. SUBJECTS:In all, 188 patients (mean 51.6 years) with 210 breast tumors (136 malignant and 74 benign) who underwent mpMRI from December 2010 to September 2014. FIELD STRENGTH/SEQUENCE:IR inversion recovert DCE-MRI dynamic contrast-enhanced magnetic resonance imaging VIBE Volume-Interpolated-Breathhold-Examination FLASH turbo fast-low-angle-shot TWIST Time-resolved angiography with stochastic Trajectories. ASSESSMENT:/sec for differentiation between benign and malignant lesions. Histopathology was the standard of reference. STATISTICAL TESTS:test, Fisher's exact test, Kruskal-Wallis test, Pearson correlation coefficient, multivariate logistic regression analysis, Hosmer-Lemeshow test of goodness-of-fit, receiver operating characteristics analysis. RESULTS:-weighted imaging does not significantly contribute to breast cancer diagnosis. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:864-874.
PMCID:6375760
PMID: 30375702
ISSN: 1522-2586
CID: 5475562
Multimodality Imaging of Breast Parenchymal Density and Correlation with Risk Assessment
Wengert, Georg J; Helbich, Thomas H; Leithner, Doris; Morris, Elizabeth A; Baltzer, Pascal A T; Pinker, Katja
PURPOSE OF REVIEW/UNASSIGNED:Breast density, or the amount of fibroglandular tissue in the breast, has become a recognized and independent marker for breast cancer risk. Public awareness of breast density as a possible risk factor for breast cancer has resulted in legislation for risk stratification purposes in many US states. This review will provide a comprehensive overview of the currently available imaging modalities for qualitative and quantitative breast density assessment and the current evidence on breast density and breast cancer risk assessment. RECENT FINDINGS/UNASSIGNED:To date, breast density assessment is mainly performed with mammography and to some extent with magnetic resonance imaging. Data indicate that computerized, quantitative techniques in comparison with subjective visual estimations are characterized by higher reproducibility and robustness. SUMMARY/UNASSIGNED:Breast density reduces the sensitivity of mammography due to a masking effect and is also a recognized independent risk factor for breast cancer. Standardized breast density assessment using automated volumetric quantitative methods has the potential to be used for risk prediction and stratification and in determining the best screening plan for each woman.
PMCID:9044508
PMID: 35496471
ISSN: 1943-4588
CID: 5475872