Fat-signal suppression in breast diffusion-weighted imaging: the Good, the Bad, and the Ugly.

OBJECTIVES: Fat-signal suppression is essential for breast diffusion magnetic resonance imaging (or diffusion-weighted MRI, DWI) as the very low diffusion coefficient of fat tends to decrease absolute diffusion coefficient (ADC) values. Among several methods, the STIR (short-tau inversion recovery) method is a popular approach, but signal suppression/attenuation is not specific to fat contrary to other methods such as SPAIR (spectral adiabatic (or attenuated) inversion recovery). This article focuses on those two techniques to illustrate the importance of appropriate fat suppression in breast DWI, briefly presenting the pros and cons of both approaches. METHODS AND RESULTS: We show here through simulation and data acquired in a dedicated breast DWI phantom made of vials with water and various concentrations of polyvinylpyrrolidone (PVP) how ADC values obtained with STIR DWI may be biased toward tissue components with the longest T1 values: ADC values obtained with STIR fat suppression may be over/underestimated depending on the T1 and ADC profile within tissues. This bias is also illustrated in two clinical examples. CONCLUSION: Fat-specific methods should be preferred over STIR for fat-signal suppression in breast DWI, such as SPAIR which also provides a higher sensitivity than STIR for lesion detection. One should remain aware, however, that efficient fat-signal suppression with SPAIR requires good B0 shimming to avoid ADC underestimation from residual fat contamination. CLINICAL RELEVANCE STATEMENT: The spectral adiabatic (or attenuated) inversion recovery (SPAIR) method should be preferred over short-tau inversion recovery (STIR) for fat suppression in breast DWI. KEY POINTS: Fat-signal suppression is essential for breast DWI; the SPAIR method is recommended. Short-tau inversion recovery (STIR) is not specific to fat; as a result, SNR is decreased and ADC values may be over- or underestimated. The STIR fat-suppression method must not be used after the injection of gadolinium-based contrast agents.

Advanced breast diffusion-weighted imaging: what are the next steps? A proposal from the EUSOBI International Breast Diffusion-weighted Imaging working group.

OBJECTIVES: This study by the EUSOBI International Breast Diffusion-weighted Imaging (DWI) working group aimed to evaluate the current and future applications of advanced DWI in breast imaging. METHODS: A literature search and a comprehensive survey of EUSOBI members to explore the clinical use and potential of advanced DWI techniques and a literature search were involved. Advanced DWI approaches such as intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), and diffusion tensor imaging (DTI) were assessed for their current status and challenges in clinical implementation. RESULTS: Although a literature search revealed an increasing number of publications and growing academic interest in advanced DWI, the survey revealed limited adoption of advanced DWI techniques among EUSOBI members, with 32% using IVIM models, 17% using non-Gaussian diffusion techniques for kurtosis analysis, and only 8% using DTI. A variety of DWI techniques are used, with IVIM being the most popular, but less than half use it, suggesting that the study identified a gap between the potential benefits of advanced DWI and its actual use in clinical practice. CONCLUSION: The findings highlight the need for further research, standardization and simplification to transition advanced DWI from a research tool to regular practice in breast imaging. The study concludes with guidelines and recommendations for future research directions and clinical implementation, emphasizing the importance of interdisciplinary collaboration in this field to improve breast cancer diagnosis and treatment. CLINICAL RELEVANCE STATEMENT: Advanced DWI in breast imaging, while currently in limited clinical use, offers promising improvements in diagnosis, staging, and treatment monitoring, highlighting the need for standardized protocols, accessible software, and collaborative approaches to promote its broader integration into routine clinical practice. KEY POINTS: Increasing number of publications on advanced DWI over the last decade indicates growing research interest. EUSOBI survey shows that advanced DWI is used primarily in research, not extensively in clinical practice. More research and standardization are needed to integrate advanced DWI into routine breast imaging practice.

Ultrafast Dynamic Contrast-Enhanced MRI of the Breast: From Theory to Practice.

The development of ultrafast dynamic contrast-enhanced (UF-DCE) MRI has occurred in tandem with fast MRI scan techniques, particularly view-sharing and compressed sensing. Understanding the strengths of each technique and optimizing the relevant parameters are essential to their implementation. UF-DCE MRI has now shifted from research protocols to becoming a part of clinical scan protocols for breast cancer. UF-DCE MRI is expected to compensate for the low specificity of abbreviated MRI by adding kinetic information from the upslope of the time-intensity curve. Because kinetic information from UF-DCE MRI is obtained from the shape and timing of the initial upslope, various new kinetic parameters have been proposed. These parameters may be associated with receptor status or prognostic markers for breast cancer. In addition to the diagnosis of malignant lesions, more emphasis has been placed on predicting and evaluating treatment response because hyper-vascularity is linked to the aggressiveness of breast cancers. In clinical practice, it is important to note that breast lesion images obtained from UF-DCE MRI are slightly different from those obtained by conventional DCE MRI in terms of morphology. A major benefit of using UF-DCE MRI is avoidance of the marked or moderate background parenchymal enhancement (BPE) that can obscure the target enhancing lesions. BPE is less prominent in the earlier phases of UF-DCE MRI, which offers better lesion-to-noise contrast. The excellent contrast of early-enhancing vessels provides a key to understanding the detailed pathological structure of tumor-associated vessels. UF-DCE MRI is normally accompanied by a large volume of image data for which automated/artificial intelligence-based processing is expected to be useful. In this review, both the theoretical and practical aspects of UF-DCE MRI are summarized. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

A multiparametric approach to predict triple-negative breast cancer including parameters derived from ultrafast dynamic contrast-enhanced MRI.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a highly proliferative breast cancer subtype. We aimed to identify TNBC among invasive cancers presenting as masses using maximum slope (MS) and time to enhancement (TTE) measured on ultrafast (UF) DCE-MRI, ADC measured on DWI, and rim enhancement on UF DCE-MRI and early-phase DCE-MRI. METHODS: This retrospective single-center study, between December 2015 and May 2020, included patients with breast cancer presenting as masses. Early-phase DCE-MRI was performed immediately after UF DCE-MRI. Interrater agreements were evaluated using the intraclass correlation coefficient (ICC) and Cohen's kappa. Univariate and multivariate logistic regression analyses of the MRI parameters, lesion size, and patient age were performed to predict TNBC and create a prediction model. The programmed death-ligand 1 (PD-L1) expression statuses of the patients with TNBCs were also evaluated. RESULTS: In total, 187 women (mean age, 58 years ± 12.9 [standard deviation]) with 191 lesions (33 TNBCs) were evaluated. The ICC for MS, TTE, ADC, and lesion size were 0.95, 0.97, 0.83, and 0.99, respectively. The kappa values of rim enhancements on UF and early-phase DCE-MRI were 0.88 and 0.84, respectively. MS on UF DCE-MRI and rim enhancement on early-phase DCE-MRI remained significant parameters after multivariate analyses. The prediction model created using these significant parameters yielded an area under the curve of 0.74 (95% CI, 0.65, 0.84). The PD-L1-expressing TNBCs tended to have higher rim enhancement rates than the non-PD-L1-expressing TNBCs. CONCLUSION: A multiparametric model using UF and early-phase DCE-MRI parameters may be a potential imaging biomarker to identify TNBCs. CLINICAL RELEVANCE STATEMENT: Prediction of TNBC or non-TNBC at an early point of diagnosis is crucial for appropriate management. This study offers the potential of UF and early-phase DCE-MRI to offer a solution to this clinical issue. KEY POINTS: • It is crucial to predict TNBC at an early clinical period. • Parameters on UF DCE-MRI and early-phase conventional DCE-MRI help in predicting TNBC. • Prediction of TNBC by MRI may be useful in determining appropriate clinical management.

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.

Diffusion MRI of the breast: Current status and future directions.

Diffusion-weighted imaging (DWI) is increasingly being incorporated into routine breast MRI protocols in many institutions worldwide, and there are abundant breast DWI indications ranging from lesion detection and distinguishing malignant from benign tumors to assessing prognostic biomarkers of breast cancer and predicting treatment response. DWI has the potential to serve as a noncontrast MR screening method. Beyond apparent diffusion coefficient (ADC) mapping, which is a commonly used quantitative DWI measure, advanced DWI models such as intravoxel incoherent motion (IVIM), non-Gaussian diffusion MRI, and diffusion tensor imaging (DTI) are extensively exploited in this field, allowing the characterization of tissue perfusion and architecture and improving diagnostic accuracy without the use of contrast agents. This review will give a summary of the clinical literature along with future directions. Level of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:70-90.

New parameters of ultrafast dynamic contrast-enhanced breast MRI using compressed sensing.

BACKGROUND: Ultrafast dynamic contrast-enhanced (UF-DCE) breast MRI is considered a promising method of accelerated breast MRI. However, the value of new kinetic parameters derived from UF-DCE need clinical evaluation. PURPOSE: To evaluate the diagnostic performance of the maximum slope (MS), time to enhancement (TTE), and time interval between arterial and venous visualization (AVI) derived from UF-DCE MRI using compressed sensing (CS). STUDY TYPE: Retrospective. POPULATION: Seventy-five patients with histologically proven breast lesions. The total number of analyzed lesions was 90 (61 malignant and 29 benign). FIELD STRENGTH/SEQUENCE: 3T MRI with UF-DCE MRI based on the 3D gradient-echo volumetric interpolated breath-hold examination (VIBE) sequence using incoherent k-space sampling combined with a CS reconstruction followed by conventional DCE MRI. ASSESSMENT: The diagnostic performance of the MS, TTE, AVI, and conventional kinetic analysis was analyzed and compared with histology. STATISTICAL TESTS: Wilcoxon rank sum test, receiver operating characteristic analysis. RESULTS: The MS was larger and the TTE and AVI were smaller for malignant lesions compared with benign lesions: MS: 29.3%/s and 18.4%/s (P < 0.001), TTE: 7.0 and 12.0 seconds (P < 0.001), AVI: 2.7 and 4.4 frames (P = 0.006) for malignant and benign lesions. The discriminating power of the MS (area under the curve [AUC], 0.76) was slightly better than that of conventional kinetic analysis (AUC, 0.69) and comparable to that of the TTE and AVI (AUC, 0.78 and 0.76 for TTE and AVI, respectively). Invasive lobular carcinoma had smaller MS (21.8%/s) among malignant lesions (29.3%/s). DATA CONCLUSION: The MS, TTE, and AVI can be used to evaluate breast lesions with clinical performance equivalent to that of conventional kinetic analysis. These parameters vary among histologies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:164-174.

Six DWI questions you always wanted to know but were afraid to ask: clinical relevance for breast diffusion MRI.

Diffusion MRI (often called diffusion-weighted imaging or DWI) has enjoyed a tremendous growth since its introduction in the mid-1980s, especially to investigate neurological disorders and in oncology. At a time when standardization and quality control appear as critical as ever to support widespread utilization, our aim was to address common fundamental questions that arise regarding results obtained with DWI. We focus on six questions taking breast DWI as an example, as breast DWI is increasingly used in clinical practice, but most of our conclusions would apply to DWI in general. We show especially that noise can act in a pernicious way specific to DWI. Ignoring such noise effects could lead to incorrect data interpretations or conclusions, of which authors and readers may be genuinely unaware. While addressing these six questions, we give practical examples of how noise effects can be understood, corrected when possible, or taken to our advantage. Key Points • Ignoring noise effects in DWI could lead to incorrect data interpretations or conclusions, of which authors and readers may be genuinely unaware. • In vivo apparent diffusion coefficient (ADC) decreases with b value, which must therefore be reported along with ADC. • Synthesized DWI boosts contrast at the expense of accurate diffusion/microstructure characterization.

Diffusion-weighted imaging of the breast-a consensus and mission statement from the EUSOBI International Breast Diffusion-Weighted Imaging working group.

The European Society of Breast Radiology (EUSOBI) established an International Breast DWI working group. The working group consists of clinical breast MRI experts, MRI physicists, and representatives from large vendors of MRI equipment, invited based upon proven expertise in breast MRI and/or in particular breast DWI, representing 25 sites from 16 countries. The aims of the working group are (a) to promote the use of breast DWI into clinical practice by issuing consensus statements and initiate collaborative research where appropriate; (b) to define necessary standards and provide practical guidance for clinical application of breast DWI; (c) to develop a standardized and translatable multisite multivendor quality assurance protocol, especially for multisite research studies; (d) to find consensus on optimal methods for image processing/analysis, visualization, and interpretation; and (e) to work collaboratively with system vendors to improve breast DWI sequences. First consensus recommendations, presented in this paper, include acquisition parameters for standard breast DWI sequences including specifications of b values, fat saturation, spatial resolution, and repetition and echo times. To describe lesions in an objective way, levels of diffusion restriction/hindrance in the breast have been defined based on the published literature on breast DWI. The use of a small ROI placed on the darkest part of the lesion on the ADC map, avoiding necrotic, noisy or non-enhancing lesion voxels is currently recommended. The working group emphasizes the need for standardization and quality assurance before ADC thresholds are applied. The working group encourages further research in advanced diffusion techniques and tailored DWI strategies for specific indications. Key Points • The working group considers breast DWI an essential part of a multiparametric breast MRI protocol and encourages its use. • Basic requirements for routine clinical application of breast DWI are provided, including recommendations on b values, fat saturation, spatial resolution, and other sequence parameters. • Diffusion levels in breast lesions are defined based on meta-analysis data and methods to obtain a reliable ADC value are detailed.

Time-dependent diffusion MRI to distinguish malignant from benign head and neck tumors.

BACKGROUND: There is growing interest in the effect of diffusion time on apparent diffusion coefficient (ADC) values in cancers; however, little evidence exists regarding its utility to differentiate malignant from benign head and neck tumors. PURPOSE: To investigate the utility of ADC value changes in distinguishing between malignant and benign head and neck tumors using the different diffusion times obtained from oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) MRI sequences. STUDY TYPE: Prospective. SUBJECTS: Thirty-one consecutive patients with suspected head and neck tumors and a phantom. FIELD STRENGTH/SEQUENCE: 3T MRI with diffusion-weighted imaging (DWI) using OGSE (effective diffusion time: 4.3 msec) and PGSE (effective diffusion time: 82.6 msec) sequences and b-values of 0 and 700 s/mm2 . ASSESSMENT: ADC values using OGSE (ADCOGSE ) and PGSE (ADCPGSE ) and relative ADC value changes between ADCOGSE and ADCPGSE . STATISTICAL TESTS: Wilcoxon test, Mann-Whitney test, and McNemar test. RESULTS: Relative ADC changes for each polyvinylpyrrolidone (PVP) and water in the phantom between OGSE and PGSE sequences were small (relative ADC change within 0.6%). Malignant tumors had significantly smaller ADCOGSE and ADCPGSE values than benign tumors (P < 0.001 and < 0.0001, respectively). Significantly larger relative ADC changes were observed in malignant compared with benign head and neck tumors (P < 0.0001). ADCPGSE values were significantly lower than ADCOGSE values in both malignant and benign head and neck tumors (0.97 vs. 1.28 × 10-3 mm2 /s: P < 0.0001 and 1.93 vs. 1.99 × 10-3 mm2 /s: P = 0.0056, respectively). Relative ADC change and ADCPGSE tended to have higher diagnostic performance than ADCOGSE , with area under the curve (AUC) values of 0.97, 0.96, and 0.89, respectively. DATA CONCLUSION: ADC values obtained using the PGSE sequence were lower than those obtained with OGSE. This difference was larger for malignant than benign tumors, suggesting differences in tissue structure (diffusion hindrance) or cell permeability, revealed by changes in diffusion time. The results underline the potential importance of reporting diffusion time for interpretation of head and neck diffusion MRI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:88-95.

Intravoxel Incoherent Motion and Quantitative Non-Gaussian Diffusion MR Imaging: Evaluation of the Diagnostic and Prognostic Value of Several Markers of Malignant and Benign Breast Lesions.

Purpose To investigate the performance of integrated approaches that combined intravoxel incoherent motion (IVIM) and non-Gaussian diffusion parameters compared with the Breast Imaging and Reporting Data System (BI-RADS) to establish multiparameter thresholds scores or probabilities by using Bayesian analysis to distinguish malignant from benign breast lesions and their correlation with molecular prognostic factors. Materials and Methods Between May 2013 and March 2015, 411 patients were prospectively enrolled and 199 patients (allocated to training [n = 99] and validation [n = 100] sets) were included in this study. IVIM parameters (flowing blood volume fraction [fIVIM] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion parameters (theoretical apparent diffusion coefficient [ADC] at b value of 0 sec/mm2 [ADC0] and kurtosis [K]) by using IVIM and kurtosis models were estimated from diffusion-weighted image series (16 b values up to 2500 sec/mm2), as well as a synthetic ADC (sADC) calculated by using b values of 200 and 1500 (sADC200-1500) and a standard ADC calculated by using b values of 0 and 800 sec/mm2 (ADC0-800). The performance of two diagnostic approaches (combined parameter thresholds and Bayesian analysis) combining IVIM and diffusion parameters was evaluated and compared with BI-RADS performance. The Mann-Whitney U test and a nonparametric multiple comparison test were used to compare their performance to determine benignity or malignancy and as molecular prognostic biomarkers and subtypes of breast cancer. Results Significant differences were found between malignant and benign breast lesions for IVIM and non-Gaussian diffusion parameters (ADC0, K, fIVIM, fIVIM · D*, sADC200-1500, and ADC0-800; P < .05). Sensitivity and specificity for the validation set by radiologists A and B were as follows: sensitivity, 94.7% and 89.5%, and specificity, 75.0% and 79.2% for sADC200-1500, respectively; sensitivity, 94.7% and 96.1%, and specificity, 75.0% and 66.7%, for the combined thresholds approach, respectively; sensitivity, 92.1% and 92.1%, and specificity, 83.3% and 66.7%, for Bayesian analysis, respectively; and sensitivity and specificity, 100% and 79.2%, for BI-RADS, respectively. The significant difference in values of sADC200-1500 in progesterone receptor status (P = .002) was noted. sADC200-1500 was significantly different between histologic subtypes (P = .006). Conclusion Approaches that combined various IVIM and non-Gaussian diffusion MR imaging parameters may provide BI-RADS-equivalent scores almost comparable to BI-RADS categories without the use of contrast agents. Non-Gaussian diffusion parameters also differed by biologic prognostic factors. © RSNA, 2017 Online supplemental material is available for this article.

Ultrafast dynamic contrast-enhanced mri of the breast using compressed sensing: breast cancer diagnosis based on separate visualization of breast arteries and veins.

PURPOSE: To evaluate the feasibility of ultrafast dynamic contrast-enhanced (UF-DCE) magnetic resonance imaging (MRI) with compressed sensing (CS) for the separate identification of breast arteries/veins and perform temporal evaluations of breast arteries and veins with a focus on the association with ipsilateral cancers. MATERIALS AND METHODS: Our Institutional Review Board approved this study with retrospective design. Twenty-five female patients who underwent UF-DCE MRI at 3T were included. UF-DCE MRI consisting of 20 continuous frames was acquired using a prototype 3D gradient-echo volumetric interpolated breath-hold sequence including a CS reconstruction: temporal resolution, 3.65 sec/frame; spatial resolution, 0.9 × 1.3 × 2.5 mm. Two readers analyzed 19 maximum intensity projection images reconstructed from subtracted images, separately identified breast arteries/veins and the earliest frame in which they were respectively visualized, and calculated the time interval between arterial and venous visualization (A-V interval) for each breast. RESULTS: In total, 49 breasts including 31 lesions (breast cancer, 16; benign lesion, 15) were identified. In 39 of the 49 breasts (breasts with cancers, 16; breasts with benign lesions, 10; breasts with no lesions, 13), both breast arteries and veins were separately identified. The A-V intervals for breasts with cancers were significantly shorter than those for breasts with benign lesions (P = 0.043) and no lesions (P = 0.007). CONCLUSION: UF-DCE MRI using CS enables the separate identification of breast arteries/veins. Temporal evaluations calculating the time interval between arterial and venous visualization might be helpful in the differentiation of ipsilateral breast cancers from benign lesions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:97-104.

Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological Tissues.

Since its introduction in the mid-1980s, diffusion magnetic resonance imaging (MRI), which measures the random motion of water molecules in tissues, revealing their microarchitecture, has become a pillar of modern neuroimaging. Its main clinical domain has been the diagnosis of acute brain stroke and neurogical disorders, but it is also used in the body for the detection and management of cancer lesions. It can also produce stunning maps of white matter tracks in the brain, with the potential to aid in the understanding of some psychiatric disorders. However, in order to exploit fully the potential of this method, a deeper understanding of the mechanisms that govern the diffusion of water in tissues is needed.

Correction: Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological Tissues.

[This corrects the article DOI: 10.1371/journal.pbio.1002203.].