AI Applications to Breast MRI: Today and Tomorrow.

In breast imaging, there is an unrelenting increase in the demand for breast imaging services, partly explained by continuous expanding imaging indications in breast diagnosis and treatment. As the human workforce providing these services is not growing at the same rate, the implementation of artificial intelligence (AI) in breast imaging has gained significant momentum to maximize workflow efficiency and increase productivity while concurrently improving diagnostic accuracy and patient outcomes. Thus far, the implementation of AI in breast imaging is at the most advanced stage with mammography and digital breast tomosynthesis techniques, followed by ultrasound, whereas the implementation of AI in breast magnetic resonance imaging (MRI) is not moving along as rapidly due to the complexity of MRI examinations and fewer available dataset. Nevertheless, there is persisting interest in AI-enhanced breast MRI applications, even as the use of and indications of breast MRI continue to expand. This review presents an overview of the basic concepts of AI imaging analysis and subsequently reviews the use cases for AI-enhanced MRI interpretation, that is, breast MRI triaging and lesion detection, lesion classification, prediction of treatment response, risk assessment, and image quality. Finally, it provides an outlook on the barriers and facilitators for the adoption of AI in breast MRI. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 6.

Assessment of Hypoxia in Breast Cancer: Emerging Functional MR Imaging and Spectroscopy Techniques and Clinical Applications.

Breast cancer is one of the most prevalent forms of cancer affecting women worldwide. Hypoxia, a condition characterized by insufficient oxygen supply in tumor tissues, is closely associated with tumor aggressiveness, resistance to therapy, and poor clinical outcomes. Accurate assessment of tumor hypoxia can guide treatment decisions, predict therapy response, and contribute to the development of targeted therapeutic interventions. Over the years, functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) techniques have emerged as promising noninvasive imaging options for evaluating hypoxia in cancer. Such techniques include blood oxygen level-dependent (BOLD) MRI, oxygen-enhanced MRI (OE) MRI, chemical exchange saturation transfer (CEST) MRI, and proton MRS (1H-MRS). These may help overcome the limitations of the routinely used dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) techniques, contributing to better diagnosis and understanding of the biological features of breast cancer. This review aims to provide a comprehensive overview of the emerging functional MRI and MRS techniques for assessing hypoxia in breast cancer, along with their evolving clinical applications. The integration of these techniques in clinical practice holds promising implications for breast cancer management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Update on DWI for Breast Cancer Diagnosis and Treatment Monitoring.

DWI is a noncontrast MRI technique that measures the diffusion of water molecules within biologic tissue. DWI is increasingly incorporated into routine breast MRI examinations. Currently, the main applications of DWI are breast cancer detection and characterization, prognostication, and prediction of treatment response to neoadjuvant chemotherapy. In addition, DWI is promising as a noncontrast MRI alternative for breast cancer screening. Problems with suboptimal resolution and image quality have restricted the mainstream use of DWI for breast imaging, but these shortcomings are being addressed through several technologic advancements. In this review, we present an up-to-date assessment of the use of DWI for breast cancer imaging, including a summary of the clinical literature and recommendations for future use.

Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study.

BACKGROUND: Monoexponential apparent diffusion coefficient (ADC) and biexponential intravoxel incoherent motion (IVIM) analysis of diffusion-weighted imaging is helpful in the characterization of breast tumors. However, repeatability/reproducibility studies across scanners and across sites are scarce. PURPOSE: To evaluate the repeatability and reproducibility of ADC and IVIM parameters (tissue diffusivity (Dt ), perfusion fraction (Fp ) and pseudo-diffusion (Dp )) within and across sites employing MRI scanners from different vendors utilizing 16-channel breast array coils in a breast diffusion phantom. STUDY TYPE: Phantom repeatability. PHANTOM: A breast phantom containing tubes of different polyvinylpyrrolidone (PVP) concentrations, water, fat, and sponge flow chambers, together with an MR-compatible liquid crystal (LC) thermometer. FIELD STRENGTH/SEQUENCE: Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. ASSESSMENT: Studies were performed twice in each of two scanners, located at different sites, on each of 2 days, resulting in four studies per scanner. ADCs of the PVP and water were normalized to the vendor-provided calibrated values at the temperature indicated by the LC thermometer for repeatability/reproducibility comparisons. STATISTICAL TESTS: ADC and IVIM repeatability and reproducibility within and across sites were estimated via the within-system coefficient of variation (wCV). Pearson correlation coefficient (r) was also computed between IVIM metrics and flow speed. A P value <0.05 was considered statistically significant. RESULTS: ADC and Dt demonstrated excellent repeatability (<2%; <3%, respectively) and reproducibility (both <5%) at the two sites. Fp and Dp exhibited good repeatability (mean of two sites 3.67% and 5.59%, respectively) and moderate reproducibility (mean of two sites 15.96% and 13.3%, respectively). The mean intersite reproducibility (%) of Fp /Dp /Dt was 50.96/13.68/5.59, respectively. Fp and Dt demonstrated high correlations with flow speed while Dp showed lower correlations. Fp correlations with flow speed were significant at both sites. DATA CONCLUSION: IVIM reproducibility results were promising and similar to ADC, particularly for Dt . The results were reproducible within both sites, and a progressive trend toward reproducibility across sites except for Fp . LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

A survey by the European Society of Breast Imaging on the implementation of breast diffusion-weighted imaging in clinical practice.

OBJECTIVES: To perform a survey among all European Society of Breast Imaging (EUSOBI) radiologist members to gather representative data regarding the clinical use of breast DWI. METHODS: An online questionnaire was developed by two board-certified radiologists, reviewed by the EUSOBI board and committees, and finally distributed among EUSOBI active and associated (not based in Europe) radiologist members. The questionnaire included 20 questions pertaining to technical preferences (acquisition time, magnet strength, breast coils, number of b values), clinical indications, imaging evaluation, and reporting. Data were analyzed using descriptive statistics, the Chi-square test of independence, and Fisher's exact test. RESULTS: Of 1411 EUSOBI radiologist members, 275/1411 (19.5%) responded. Most (222/275, 81%) reported using DWI as part of their routine protocol. Common indications for DWI include lesion characterization (using an ADC threshold of 1.2-1.3 × 10-3 mm2/s) and prediction of response to chemotherapy. Members most commonly acquire two separate b values (114/217, 53%), with b value = 800 s/mm2 being the preferred value for appraisal among those acquiring more than two b values (71/171, 42%). Most did not use synthetic b values (169/217, 78%). While most mention hindered diffusion in the MRI report (161/213, 76%), only 142/217 (57%) report ADC values. CONCLUSION: The utilization of DWI in clinical practice among EUSOBI radiologists who responded to the survey is generally in line with international recommendations, with the main application being the differentiation of benign and malignant enhancing lesions, treatment response assessment, and prediction of response to chemotherapy. Report integration of qualitative and quantitative DWI data is not uniform. KEY POINTS: • Clinical performance of breast DWI is in good agreement with the current recommendations of the EUSOBI International Breast DWI working group. • Breast DWI applications in clinical practice include the differentiation of benign and malignant enhancing, treatment response assessment, and prediction of response to chemotherapy. • Report integration of DWI results is not uniform.

Diagnostic value of diffusion-weighted imaging with synthetic b-values in breast tumors: comparison with dynamic contrast-enhanced and multiparametric MRI.

OBJECTIVES: To assess DWI for tumor visibility and breast cancer detection by the addition of different synthetic b-values. METHODS: Eighty-four consecutive women who underwent a breast-multiparametric-MRI (mpMRI) with enhancing lesions on DCE-MRI (BI-RADS 2-5) were included in this IRB-approved retrospective study from September 2018 to March 2019. Three readers evaluated DW acquired b-800 and synthetic b-1000, b-1200, b-1500, and b-1800 s/mm2 images for lesion visibility and preferred b-value based on lesion conspicuity. Image quality (1-3 scores) and breast composition (BI-RADS) were also recorded. Diagnostic parameters for DWI were determined using a 1-5 malignancy score based on qualitative imaging parameters (acquired + preferred synthetic b-values) and ADC values. BI-RADS classification was used for DCE-MRI and quantitative ADC values + BI-RADS were used for mpMRI. RESULTS: Sixty-four malignant (average = 23 mm) and 39 benign (average = 8 mm) lesions were found in 80 women. Although b-800 achieved the best image quality score, synthetic b-values 1200-1500 s/mm2 were preferred for lesion conspicuity, especially in dense breast. b-800 and synthetic b-1000/b-1200 s/mm2 values allowed the visualization of 84-90% of cancers visible with DCE-MRI performing better than b-1500/b-1800 s/mm2. DWI was more specific (86.3% vs 65.7%, p < 0.001) but less sensitive (62.8% vs 90%, p < 0.001) and accurate (71% vs 80.7%, p = 0.003) than DCE-MRI for breast cancer detection, where mpMRI was the most accurate modality accounting for less false positive cases. CONCLUSION: The addition of synthetic b-values enhances tumor conspicuity and could potentially improve tumor visualization particularly in dense breast. However, its supportive role for DWI breast cancer detection is still not definite. KEY POINTS: • The addition of synthetic b-values (1200-1500 s/mm2) to acquired DWI afforded a better lesion conspicuity without increasing acquisition time and was particularly useful in dense breasts. • Despite the use of synthetic b-values, DWI was less sensitive and accurate than DCE-MRI for breast cancer detection. • A multiparametric MRI modality still remains the best approach having the highest accuracy for breast cancer detection and thus reducing the number of unnecessary biopsies.

Improved characterization of sub-centimeter enhancing breast masses on MRI with radiomics and machine learning in BRCA mutation carriers.

OBJECTIVES: To investigate whether radiomics features extracted from MRI of BRCA-positive patients with sub-centimeter breast masses can be coupled with machine learning to differentiate benign from malignant lesions using model-free parameter maps. METHODS: In this retrospective study, BRCA-positive patients who had an MRI from November 2013 to February 2019 that led to a biopsy (BI-RADS 4) or imaging follow-up (BI-RADS 3) for sub-centimeter lesions were included. Two radiologists assessed all lesions independently and in consensus according to BI-RADS. Radiomics features were calculated using open-source CERR software. Univariate analysis and multivariate modeling were performed to identify significant radiomics features and clinical factors to be included in a machine learning model to differentiate malignant from benign lesions. RESULTS: Ninety-six BRCA mutation carriers (mean age at biopsy = 45.5 ± 13.5 years) were included. Consensus BI-RADS classification assessment achieved a diagnostic accuracy of 53.4%, sensitivity of 75% (30/40), specificity of 42.1% (32/76), PPV of 40.5% (30/74), and NPV of 76.2% (32/42). The machine learning model combining five parameters (age, lesion location, GLCM-based correlation from the pre-contrast phase, first-order coefficient of variation from the 1st post-contrast phase, and SZM-based gray level variance from the 1st post-contrast phase) achieved a diagnostic accuracy of 81.5%, sensitivity of 63.2% (24/38), specificity of 91.4% (64/70), PPV of 80.0% (24/30), and NPV of 82.1% (64/78). CONCLUSIONS: Radiomics analysis coupled with machine learning improves the diagnostic accuracy of MRI in characterizing sub-centimeter breast masses as benign or malignant compared with qualitative morphological assessment with BI-RADS classification alone in BRCA mutation carriers. KEY POINTS: • Radiomics and machine learning can help differentiate benign from malignant breast masses even if the masses are small and morphological features are benign. • Radiomics and machine learning analysis showed improved diagnostic accuracy, specificity, PPV, and NPV compared with qualitative morphological assessment alone.

Radiomic signatures with contrast-enhanced magnetic resonance imaging for the assessment of breast cancer receptor status and molecular subtypes: initial results.

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.

Limited role of DWI with apparent diffusion coefficient mapping in breast lesions presenting as non-mass enhancement on dynamic contrast-enhanced MRI.

BACKGROUND: Available data proving the value of DWI for breast cancer diagnosis is mainly for enhancing masses; DWI may be less sensitive and specific in non-mass enhancement (NME) lesions. The objective of this study was to assess the diagnostic accuracy of DWI using different ROI measurement approaches and ADC metrics in breast lesions presenting as NME lesions on dynamic contrast-enhanced (DCE) MRI. METHODS: In this retrospective study, 95 patients who underwent multiparametric MRI with DCE and DWI from September 2007 to July 2013 and who were diagnosed with a suspicious NME (BI-RADS 4/5) were included. Twenty-nine patients were excluded for lesion non-visibility on DWI (n = 24: 12 benign and 12 malignant) and poor DWI quality (n = 5: 1 benign and 4 malignant). Two readers independently assessed DWI and DCE-MRI findings in two separate randomized readings using different ADC metrics and ROI approaches. NME lesions were classified as either benign (> 1.3 × 10-3 mm2/s) or malignant (≤ 1.3 × 10-3 mm2/s). Histopathology was the standard of reference. ROC curves were plotted, and AUCs were determined. Concordance correlation coefficient (CCC) was measured. RESULTS: There were 39 malignant (59%) and 27 benign (41%) lesions in 66 (65 women, 1 man) patients (mean age, 51.8 years). The mean ADC value of the darkest part of the tumor (Dptu) achieved the highest diagnostic accuracy, with AUCs of up to 0.71. Inter-reader agreement was highest with Dptu ADC max (CCC 0.42) and lowest with the point tumor (Ptu) ADC min (CCC = - 0.01). Intra-reader agreement was highest with Wtu ADC mean (CCC = 0.44 for reader 1, 0.41 for reader 2), but this was not associated with the highest diagnostic accuracy. CONCLUSIONS: Diagnostic accuracy of DWI with ADC mapping is limited in NME lesions. Thirty-one percent of lesions presenting as NME on DCE-MRI could not be evaluated with DWI, and therefore, DCE-MRI remains indispensable. Best results were achieved using Dptu 2D ROI measurement and ADC mean.

Clinical applications of breast cancer metabolomics using high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H MRS): systematic scoping review.

INTRODUCTION: Breast cancer is a heterogeneous disease with different prognoses and responses to systemic treatment depending on its molecular characteristics, which makes it imperative to develop new biomarkers for an individualized diagnosis and personalized oncological treatment. Ex vivo high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H MRS) is the most common technique for metabolic quantification in human surgical and biopsy tissue specimens. OBJECTIVE: To perform a review of the current available literature on the clinical applications of HRMAS 1H MRS metabolic analysis in tissue samples of breast cancer patients. METHODS: This systematic scoping review included original research papers published in the English language in peer-reviewed journals. Study selection was performed independently by two reviewers and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. RESULTS: The literature search returned 159 studies and 26 papers were included as part of this systematic review. There was considerable variation regarding tissue type, aims, and statistical analysis methods across the different studies. To facilitate the interpretation of the results, the included studies were grouped according to their aims or main outcomes into: feasibility and tumor diagnosis (n = 6); tumor heterogeneity (n = 2); correlation with proteomics/transcriptomics (n = 3); correlation with prognostic factors (n = 11); and response evaluation to NAC (n = 4). CONCLUSION: There is a lot of potential in including metabolic information of breast cancer tissue obtained with HRMAS 1H MRS. To date, studies show that metabolic concentrations quantified by this technique can be related to the diagnosis, prognosis, and treatment response in breast cancer patients.

A multiparametric [18F]FDG PET/MRI diagnostic model including imaging biomarkers of the tumor and contralateral healthy breast tissue aids breast cancer diagnosis.

PURPOSE: To develop a multiparametric [18F]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: In this prospective study and retrospective data analysis, 141 patients (mean 57 years) with an imaging abnormality detected on mammography and/or ultrasound (BI-RADS 4/5) underwent combined multiparametric [18F]FDG PET/MRI with PET/computed tomography and multiparametric MRI of the breast at 3 T. Images were evaluated and the following were recorded: for the tumor, BI-RADS descriptors on dynamic contrast-enhanced (DCE)-MRI, mean apparent diffusion co-efficient (ADCmean) on diffusion-weighted imaging (DWI), and maximum standard uptake value (SUVmax) on [18F]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: A multiparametric [18F]FDG PET/MRI diagnostic model incorporating both qualitative and quantitative parameters of the tumor and the healthy contralateral tissue aids breast cancer diagnosis.

Proton MR spectroscopy in the breast: Technical innovations and clinical applications.

Proton magnetic resonance spectroscopy (MRS) is a promising noninvasive diagnostic technique for investigation of breast cancer metabolism. Spectroscopic imaging data may be obtained following contrast-enhanced MRI by applying the point-resolved spectroscopy sequence (PRESS) or the stimulated echo acquisition mode (STEAM) sequence from the MR voxel encompassing the breast lesion. Total choline signal (tCho) measured in vivo using either a qualitative or quantitative approach has been used as a diagnostic test in the workup of malignant breast lesions. In addition to tCho metabolites, other relevant metabolites, including multiple lipids, can be detected and monitored. MRS has been heavily investigated as an adjunct to morphologic and dynamic MRI to improve diagnostic accuracy in breast cancer, obviating unnecessary benign biopsies. Besides its use in the staging of breast cancer, other promising applications have been recently investigated, including the assessment of treatment response and therapy monitoring. This review provides guidance on spectroscopic acquisition and quantification methods and highlights current and evolving clinical applications of proton MRS. Level of Evidence 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

Multiparametric MRI model with dynamic contrast-enhanced and diffusion-weighted imaging enables breast cancer diagnosis with high accuracy.

BACKGROUND: The MRI Breast Imaging-Reporting and Data System (BI-RADS) lexicon recommends that a breast MRI protocol contain T2 -weighted and dynamic contrast-enhanced (DCE) MRI sequences. The addition of diffusion-weighted imaging (DWI) significantly improves diagnostic accuracy. This study aims to clarify which descriptors from DCE-MRI, DWI, and T2 -weighted imaging are most strongly associated with a breast cancer diagnosis. PURPOSE/HYPOTHESIS: To develop a multiparametric MRI (mpMRI) model for breast cancer diagnosis incorporating American College of Radiology (ACR) BI-RADS recommended descriptors for breast MRI with DCE, T2 -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: Two radiologists in consensus and another radiologist independently evaluated the mpMRI data. Characteristics for mass (n = 182) and nonmass (n = 28) lesions were recorded on DCE and T2 -weighted imaging according to BI-RADS, as well as DWI descriptors. Two separate models were analyzed, using DCE-MRI BI-RADS descriptors, T2 -weighted imagines, and ADCmean as either a continuous or binary form using a previously published ADC cutoff value of ≤1.25 × 10-3 mm2 /sec for differentiation between benign and malignant lesions. Histopathology was the standard of reference. STATISTICAL TESTS: χ2 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: In Model 1, ADCmean (P = 0.0031), mass margins with DCE (P = 0.0016), and delayed enhancement with DCE (P = 0.0016) were significantly and independently associated with breast cancer diagnosis; Model 2 identified ADCmean (P = 0.0031), mass margins with DCE (P = 0.0012), initial enhancement (P = 0.0422), and delayed enhancement with DCE (P = 0.0065) to be significantly independently associated with breast cancer diagnosis. T2 -weighted imaging variables were not included in the final models. DATA CONCLUSION: mpMRI with DCE-MRI and DWI with ADC mapping enables accurate breast cancer diagnosis. A model using quantitative and qualitative descriptors from DCE-MRI and DWI identifies breast cancer with a high diagnostic accuracy. T2 -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.

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.

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: 3 T, readout-segmented echo planar imaging (rsEPI) with IR fat suppression, dynamic contrast-enhanced (DCE) T1 -weighted imaging, T2 -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.

Quantitative in vivo proton MR spectroscopic assessment of lipid metabolism: Value for breast cancer diagnosis and prognosis.

BACKGROUND: Breast magnetic resonance spectroscopy (1 H-MRS) has been largely based on choline metabolites; however, other relevant metabolites can be detected and monitored. PURPOSE: To investigate whether lipid metabolite concentrations detected with 1 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: Dynamic contrast-enhanced MRI at 1.5 T: sagittal 3D spoiled gradient recalled sequence with fat saturation, flip angle = 10°, repetition time / echo time (TR/TE) = 7.4/4.2 msec, slice thickness = 3.0 mm, field of view (FOV) = 20 cm, and matrix size = 256 × 192. 1 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: There were 111 malignant and 57 benign lesions. Mean voxel size was 4.4 ± 4.6 cm3 . 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: Quantitative in vivo 1 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.

MRI evaluation of axillary and intramammary lymph nodes in the postoperative period.

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.

Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial.

BACKGROUND: Diffuse intrinsic pontine glioma is one of the deadliest central nervous system tumours of childhood, with a median overall survival of less than 12 months. Convection-enhanced delivery has been proposed as a means to efficiently deliver therapeutic agents directly into the brainstem while minimising systemic exposure and associated toxic effects. We did this study to evaluate the safety of convection-enhanced delivery of a radioimmunotherapy agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma. METHODS: We did a phase 1, single-arm, single-centre, dose-escalation study at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). Eligible patients were aged 3-21 years and had diffuse intrinsic pontine glioma as diagnosed by consensus of a multidisciplinary paediatric neuro-oncology team; a Lansky (patients <16 years of age) or Karnofsky (patients ≥16 years) performance score of at least 50 at study entry; a minimum weight of 8 kg; and had completed external beam radiation therapy (54·0-59·4 Gy at 1·8 Gy per fraction over 30-33 fractions) at least 4 weeks but no more than 14 weeks before enrolment. Seven dose-escalation cohorts were planned based on standard 3 + 3 rules: patients received a single infusion of 9·25, 18·5, 27·75, 37, 92·5, 120·25, or 148 MBq, respectively, at a concentration of about 37 MBq/mL by convection-enhanced delivery of the radiolabelled antibody [124I]-8H9. The primary endpoint was identification of the maximum tolerated dose. The analysis of the primary endpoint was done in the per-protocol population (patients who received the full planned dose of treatment), and all patients who received any dose of study treatment were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01502917, and is ongoing with an expanded cohort. FINDINGS: From April 5, 2012, to Oct 8, 2016, 28 children were enrolled and treated in the trial, of whom 25 were evaluable for the primary endpoint. The maximum tolerated dose was not reached as no dose-limiting toxicities were observed. One (4%) of 28 patients had treatment-related transient grade 3 hemiparesis and one (4%) had grade 3 skin infection. No treatment-related grade 4 adverse events or deaths occurred. Estimated volumes of distribution (Vd) were linearly dependent on volumes of infusion (Vi) and ranged from 1·5 to 20·1 cm3, with a mean Vd/Vi ratio of 3·4 (SD 1·2). The mean lesion absorbed dose was 0·39 Gy/MBq 124I (SD 0·20). Systemic exposure was negligible, with an average lesion-to-whole body ratio of radiation absorbed dose higher than 1200. INTERPRETATION: Convection-enhanced delivery in the brainstem of children with diffuse intrinsic pontine glioma who have previously received radiation therapy seems to be a rational and safe therapeutic strategy. PET-based dosimetry of the radiolabelled antibody [124I]-8H9 validated the principle of using convection-enhanced delivery in the brain to achieve high intra-lesional dosing with negligible systemic exposure. This therapeutic strategy warrants further development for children with diffuse intrinsic pontine glioma. FUNDING: National Institutes of Health, The Dana Foundation, The Cure Starts Now, Solving Kids' Cancer, The Lyla Nsouli Foundation, Cookies for Kids' Cancer, The Cristian Rivera Foundation, Battle for a Cure, Cole Foundation, Meryl & Charles Witmer Charitable Foundation, Tuesdays with Mitch Charitable Foundation, and Memorial Sloan Kettering Cancer Center.

Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.

PURPOSE: To measure the apparent diffusion coefficient (ADC) values in estrogen receptor-positive (ER+) and axillary lymph node-negative (LN-) invasive breast cancer and investigate the correlation of ADC with Oncotype Dx test recurrence scores (ODxRS). MATERIALS AND METHODS: This was a Health Insurance Portability and Accountability Act (HIPAA)-compliant single-site retrospective study. Patients underwent preoperative 3.0T MRI scans with additional diffusion-weighted imaging sequential scans (b = 0, 600 and b = 0, 1000 s/mm2 ) from January 2011 to 2013. The study population included 31 ER+/LN- invasive breast cancers, which underwent ODxRS genomic testing. ADC600 and ADC1000 parametric maps were generated, and ADC values were calculated from a user-drawn region of interest. ODxRS predicts 10-year recurrence risk in individual patients: low (RS <18), intermediate (RS: 18-30), or high (RS >30). All breast lesions, including subgroups of invasive ductal carcinoma (IDC) lesions and mass-only lesions were dichotomized by RS scores, low-risk versus intermediate/high-risk, and statistical analysis was performed using Mann-Whitney's test (statistical significance at P < 0.05) and receiver operating characteristic (ROC) curves. Multivariate analysis was also performed. RESULTS: Invasive breast cancers, when scored as low-risk by ODxRS, had significantly higher ADC values compared with intermediate/high-risk lesions for both ADC600 (P = 0.007) and ADC1000 (P = 0.008) mean values. This was true both when analyzing only mass-lesions (P = 0.03 and 0.01) or only IDCs (P = 0.001 and 0.009). CONCLUSION: Preliminary findings suggest that lesion ADC values correlate with recurrence risk likelihood stratified using ODxRS. Hence, ADC is a potential surrogate biomarker for tumor aggressiveness. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:401-409.

Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of background parenchymal enhancement, amount of fibroglandular tissue and menopausal status on breast cancer diagnosis.

OBJECTIVES: To investigate the impact of background parenchymal enhancement (BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent diffusion coefficient (ADC) values in differentiation between malignant and benign lesions. METHODS: In this HIPAA-compliant study, mean ADC values of 218 malignant and 130 benign lesions from 288 patients were retrospectively evaluated. The differences in mean ADC values between benign and malignant lesions were calculated within groups stratified by BPE level (high/low), amount of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal). Sensitivities and specificities for distinguishing malignant from benign lesions within different groups were compared for statistical significance. RESULTS: The mean ADC value for malignant lesions was significantly lower compared to that for benign lesions (1.07±0.21 x 10-3 mm2/s vs. 1.53±0.26 x 10-3 mm2/s) (p<0.0001). Using the optimal cut-off point of 1.30 x 10-3 mm2/s, an area under the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %. There was no statistically significant difference in sensitivities and specificities of ADC values between different groups stratified by BPE level, amount of FGT or menopausal status. CONCLUSIONS: Differentiation between benign and malignant lesions on ADC values is not significantly affected by BPE level, amount of FGT or menopausal status. KEY POINTS: • ADC allows differentiation between benign and malignant lesions. • ADC is useful for breast cancer diagnosis despite different patient characteristics. • BPE, FGT or menopause do not significantly affect sensitivity and specificity.