Deuterium MR spectroscopy: potential applications in oncology research.

Metabolic imaging in clinical practice has long relied on PET with fluorodeoxyglucose (FDG), a radioactive tracer. However, this conventional method presents inherent limitations such as exposure to ionizing radiation and potential diagnostic uncertainties, particularly in organs with heightened glucose uptake like the brain. This review underscores the transformative potential of traditional deuterium MR spectroscopy (MRS) when integrated with gradient techniques, culminating in an advanced metabolic imaging modality known as deuterium MRI (DMRI). While recent advancements in hyperpolarized MRS hold promise for metabolic analysis, their widespread clinical usage is hindered by cost constraints and the availability of hyperpolarizer devices or facilities. DMRI, also denoted as deuterium metabolic imaging (DMI), represents a pioneering, single-shot, and noninvasive paradigm that fuses conventional MRS with nonradioactive deuterium-labelled substrates. Extensively tested in animal models and patient cohorts, particularly in cases of brain tumours, DMI's standout feature lies in its seamless integration into standard clinical MRI scanners, necessitating only minor adjustments such as radiofrequency coil tuning to the deuterium frequency. DMRI emerges as a versatile tool for quantifying crucial metabolites in clinical oncology, including glucose, lactate, glutamate, glutamine, and characterizing IDH mutations. Its potential applications in this domain are broad, spanning diagnostic profiling, treatment response monitoring, and the identification of novel therapeutic targets across diverse cancer subtypes.

AI-enhanced Mammography With Digital Breast Tomosynthesis for Breast Cancer Detection: Clinical Value and Comparison With Human Performance.

Purpose To compare two deep learning-based commercially available artificial intelligence (AI) systems for mammography with digital breast tomosynthesis (DBT) and benchmark them against the performance of radiologists. Materials and Methods This retrospective study included consecutive asymptomatic patients who underwent mammography with DBT (2019-2020). Two AI systems (Transpara 1.7.0 and ProFound AI 3.0) were used to evaluate the DBT examinations. The systems were compared using receiver operating characteristic (ROC) analysis to calculate the area under the ROC curve (AUC) for detecting malignancy overall and within subgroups based on mammographic breast density. Breast Imaging Reporting and Data System results obtained from standard-of-care human double-reading were compared against AI results with use of the DeLong test. Results Of 419 female patients (median age, 60 years [IQR, 52-70 years]) included, 58 had histologically proven breast cancer. The AUC was 0.86 (95% CI: 0.85, 0.91), 0.93 (95% CI: 0.90, 0.95), and 0.98 (95% CI: 0.96, 0.99) for Transpara, ProFound AI, and human double-reading, respectively. For Transpara, a rule-out criterion of score 7 or lower yielded 100% (95% CI: 94.2, 100.0) sensitivity and 60.9% (95% CI: 55.7, 66.0) specificity. The rule-in criterion of higher than score 9 yielded 96.6% sensitivity (95% CI: 88.1, 99.6) and 78.1% specificity (95% CI: 73.8, 82.5). For ProFound AI, a rule-out criterion of lower than score 51 yielded 100% sensitivity (95% CI: 93.8, 100) and 67.0% specificity (95% CI: 62.2, 72.1). The rule-in criterion of higher than score 69 yielded 93.1% (95% CI: 83.3, 98.1) sensitivity and 82.0% (95% CI: 77.9, 86.1) specificity. Conclusion Both AI systems showed high performance in breast cancer detection but lower performance compared with human double-reading. Keywords: Mammography, Breast, Oncology, Artificial Intelligence, Deep Learning, Digital Breast Tomosynthesis © RSNA, 2024.

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.

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.

BI-RADS Category Assignments by GPT-3.5, GPT-4, and Google Bard: A Multilanguage Study.

Background The performance of publicly available large language models (LLMs) remains unclear for complex clinical tasks. Purpose To evaluate the agreement between human readers and LLMs for Breast Imaging Reporting and Data System (BI-RADS) categories assigned based on breast imaging reports written in three languages and to assess the impact of discordant category assignments on clinical management. Materials and Methods This retrospective study included reports for women who underwent MRI, mammography, and/or US for breast cancer screening or diagnostic purposes at three referral centers. Reports with findings categorized as BI-RADS 1-5 and written in Italian, English, or Dutch were collected between January 2000 and October 2023. Board-certified breast radiologists and the LLMs GPT-3.5 and GPT-4 (OpenAI) and Bard, now called Gemini (Google), assigned BI-RADS categories using only the findings described by the original radiologists. Agreement between human readers and LLMs for BI-RADS categories was assessed using the Gwet agreement coefficient (AC1 value). Frequencies were calculated for changes in BI-RADS category assignments that would affect clinical management (ie, BI-RADS 0 vs BI-RADS 1 or 2 vs BI-RADS 3 vs BI-RADS 4 or 5) and compared using the McNemar test. Results Across 2400 reports, agreement between the original and reviewing radiologists was almost perfect (AC1 = 0.91), while agreement between the original radiologists and GPT-4, GPT-3.5, and Bard was moderate (AC1 = 0.52, 0.48, and 0.42, respectively). Across human readers and LLMs, differences were observed in the frequency of BI-RADS category upgrades or downgrades that would result in changed clinical management (118 of 2400 [4.9%] for human readers, 611 of 2400 [25.5%] for Bard, 573 of 2400 [23.9%] for GPT-3.5, and 435 of 2400 [18.1%] for GPT-4; P < .001) and that would negatively impact clinical management (37 of 2400 [1.5%] for human readers, 435 of 2400 [18.1%] for Bard, 344 of 2400 [14.3%] for GPT-3.5, and 255 of 2400 [10.6%] for GPT-4; P < .001). Conclusion LLMs achieved moderate agreement with human reader-assigned BI-RADS categories across reports written in three languages but also yielded a high percentage of discordant BI-RADS categories that would negatively impact clinical management. © RSNA, 2024 Supplemental material is available for this article.

Artificial Intelligence-Enhanced Breast MRI: Applications in Breast Cancer Primary Treatment Response Assessment and Prediction.

ABSTRACT: Primary systemic therapy (PST) is the treatment of choice in patients with locally advanced breast cancer and is nowadays also often used in patients with early-stage breast cancer. Although imaging remains pivotal to assess response to PST accurately, the use of imaging to predict response to PST has the potential to not only better prognostication but also allow the de-escalation or omission of potentially toxic treatment with undesirable adverse effects, the accelerated implementation of new targeted therapies, and the mitigation of surgical delays in selected patients. In response to the limited ability of radiologists to predict response to PST via qualitative, subjective assessments of tumors on magnetic resonance imaging (MRI), artificial intelligence-enhanced MRI with classical machine learning, and in more recent times, deep learning, have been used with promising results to predict response, both before the start of PST and in the early stages of treatment. This review provides an overview of the current applications of artificial intelligence to MRI in assessing and predicting response to PST, and discusses the challenges and limitations of their clinical implementation.

Current Status of Cancer Genomics and Imaging Phenotypes: What Radiologists Need to Know.

Ongoing discoveries in cancer genomics and epigenomics have revolutionized clinical oncology and precision health care. This knowledge provides unprecedented insights into tumor biology and heterogeneity within a single tumor, among primary and metastatic lesions, and among patients with the same histologic type of cancer. Large-scale genomic sequencing studies also sparked the development of new tumor classifications, biomarkers, and targeted therapies. Because of the central role of imaging in cancer diagnosis and therapy, radiologists need to be familiar with the basic concepts of genomics, which are now becoming the new norm in oncologic clinical practice. By incorporating these concepts into clinical practice, radiologists can make their imaging interpretations more meaningful and specific, facilitate multidisciplinary clinical dialogue and interventions, and provide better patient-centric care. This review article highlights basic concepts of genomics and epigenomics, reviews the most common genetic alterations in cancer, and discusses the implications of these concepts on imaging by organ system in a case-based manner. This information will help stimulate new innovations in imaging research, accelerate the development and validation of new imaging biomarkers, and motivate efforts to bring new molecular and functional imaging methods to clinical radiology. Keywords: Oncology, Cancer Genomics, Epignomics, Radiogenomics, Imaging Markers Supplemental material is available for this article. © RSNA, 2023.

Evaluation of cancer outcome assessment using MRI: A review of deep-learning methods.

Accurate evaluation of tumor response to treatment is critical to allow personalized treatment regimens according to the predicted response and to support clinical trials investigating new therapeutic agents by providing them with an accurate response indicator. Recent advances in medical imaging, computer hardware, and machine-learning algorithms have resulted in the increased use of these tools in the field of medicine as a whole and specifically in cancer imaging for detection and characterization of malignant lesions, prognosis, and assessment of treatment response. Among the currently available imaging techniques, magnetic resonance imaging (MRI) plays an important role in the evaluation of treatment assessment of many cancers, given its superior soft-tissue contrast and its ability to allow multiplanar imaging and functional evaluation. In recent years, deep learning (DL) has become an active area of research, paving the way for computer-assisted clinical and radiological decision support. DL can uncover associations between imaging features that cannot be visually identified by the naked eye and pertinent clinical outcomes. The aim of this review is to highlight the use of DL in the evaluation of tumor response assessed on MRI. In this review, we will first provide an overview of common DL architectures used in medical imaging research in general. Then, we will review the studies to date that have applied DL to magnetic resonance imaging for the task of treatment response assessment. Finally, we will discuss the challenges and opportunities of using DL within the clinical workflow.

Limited value of multiparametric MRI with dynamic contrast-enhanced and diffusion-weighted imaging in non-mass enhancing breast tumors.

PURPOSE: To investigate the diagnostic value of multiparametric MRI (mpMRI) including dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in non-mass enhancing breast tumors. METHOD: Patients who underwent mpMRI, who were diagnosed with a suspicious non-mass enhancement (NME) on DCE-MRI (BI-RADS 4/5), and who subsequently underwent image-guided biopsy were retrospectively included. Two radiologists independently evaluated all NMEs, on both DCE-MR images and high-b-value DW images. Different mpMRI reading approaches were evaluated: 1) with a fixed apparent diffusion coefficient (ADC) threshold (<1.3 malignant, ≥1.3 benign) based on the recommendation by the European Society of Breast Imaging (EUSOBI); 2) with a fixed ADC threshold (<1.5 malignant, ≥1.5 benign) based on recently published trial data; 3) with an ADC threshold adapted to the assigned BI-RADS classification using a previously published reading method; and 4) with individually determined best thresholds for each reader. RESULTS: The final study sample consisted of 66 lesions in 66 patients. DCE-MRI alone had the highest sensitivity for breast cancer detection (94.8-100 %), outperforming all mpMRI reading approaches (R1 74.4-87.1 %, R2 71.7-94.8 %) and DWI alone (R1 74.4 %, R2 79.4 %). The adapted approach achieved the best specificity for both readers (85.1 %), resulting in the best diagnostic accuracy for R1 (86.5 %) but a moderate diagnostic accuracy for R2 (77.2 %). CONCLUSION: mpMRI has limited added diagnostic value to DCE-MRI in the assessment of NME.

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.

Breast Lesion Classification with Multiparametric Breast MRI Using Radiomics and Machine Learning: A Comparison with Radiologists' Performance.

This multicenter retrospective study compared the performance of radiomics analysis coupled with machine learning (ML) with that of radiologists for the classification of breast tumors. A total of 93 consecutive women (mean age: 49 ± 12 years) with 104 histopathologically verified enhancing lesions (mean size: 22.8 ± 15.1 mm), classified as suspicious on multiparametric breast MRIs were included. Two experienced breast radiologists assessed all of the lesions, assigning a Breast Imaging Reporting and Database System (BI-RADS) suspicion category, providing a diffusion-weighted imaging (DWI) score based on lesion signal intensity, and determining the apparent diffusion coefficient (ADC). Ten predictive models for breast lesion discrimination were generated using radiomic features extracted from the multiparametric MRI. The area under the receiver operating curve (AUC) and the accuracy were compared using McNemar's test. Multiparametric radiomics with DWI score and BI-RADS (accuracy = 88.5%; AUC = 0.93) and multiparametric radiomics with ADC values and BI-RADS (accuracy= 88.5%; AUC = 0.96) models showed significant improvements in diagnostic accuracy compared to the multiparametric radiomics (DWI + DCE data) model (p = 0.01 and p = 0.02, respectively), but performed similarly compared to the multiparametric assessment by radiologists (accuracy = 85.6%; AUC = 0.03; p = 0.39). In conclusion, radiomics analysis coupled with the ML of multiparametric MRI could assist in breast lesion discrimination, especially for less experienced readers of breast MRIs.

Radiologist-Level Performance by Using Deep Learning for Segmentation of Breast Cancers on MRI Scans.

PURPOSE: To develop a deep network architecture that would achieve fully automated radiologist-level segmentation of cancers at breast MRI. MATERIALS AND METHODS: In this retrospective study, 38 229 examinations (composed of 64 063 individual breast scans from 14 475 patients) were performed in female patients (age range, 12-94 years; mean age, 52 years ± 10 [standard deviation]) who presented between 2002 and 2014 at a single clinical site. A total of 2555 breast cancers were selected that had been segmented on two-dimensional (2D) images by radiologists, as well as 60 108 benign breasts that served as examples of noncancerous tissue; all these were used for model training. For testing, an additional 250 breast cancers were segmented independently on 2D images by four radiologists. Authors selected among several three-dimensional (3D) deep convolutional neural network architectures, input modalities, and harmonization methods. The outcome measure was the Dice score for 2D segmentation, which was compared between the network and radiologists by using the Wilcoxon signed rank test and the two one-sided test procedure. RESULTS: The highest-performing network on the training set was a 3D U-Net with dynamic contrast-enhanced MRI as input and with intensity normalized for each examination. In the test set, the median Dice score of this network was 0.77 (interquartile range, 0.26). The performance of the network was equivalent to that of the radiologists (two one-sided test procedures with radiologist performance of 0.69-0.84 as equivalence bounds, P < .001 for both; n = 250). CONCLUSION: When trained on a sufficiently large dataset, the developed 3D U-Net performed as well as fellowship-trained radiologists in detailed 2D segmentation of breast cancers at routine clinical MRI.Keywords: MRI, Breast, Segmentation, Supervised Learning, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning AlgorithmsPublished under a CC BY 4.0 license. Supplemental material is available for this article.

Yield of flow cytometry in addition to cytology for lymph node sampling in patients with incidental axillary adenopathy without a concurrent diagnosis of primary breast malignancy.

PURPOSE: Non-specific lymphadenopathy is increasingly being reported especially given the COVID-19 vaccination campaign and is a diagnostic dilemma especially in oncology patients. The purpose of this study was to evaluate the diagnostic accuracy and discordance rate between fine-needle aspiration (FNA) cytology and flow cytometry (FC) immunophenotyping in axillary FNA in patients with morphologically abnormal axillary lymph nodes on imaging and no concurrent diagnosis of primary breast malignancy. METHODS: This retrospective study included 222 patients who underwent screening or diagnostic axillary ultrasound that yielded suspicious lymphadenopathy without concurrent or recent prior diagnosis of breast cancer and who had subsequent image-guided axillary FNA and FC. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value (PPV and NPV) were reported for FNA with cytology alone, and FC alone, and in combination. Discordance rate between FNA cytology and FC was assessed. Discordant cases were evaluated with histology or clinical and imaging follow-up. RESULTS: Diagnostic sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 88%, 92%, 77%, 96%, and 91%, for FNA alone, 98%, 98%, 92%, 99%, and 98% for FC alone, and 100%, 92%, 79%, 100%, and 94% when combined. The overall discordance rate between FNA and FC was 7% (16/222). 7/16 (44%) patients with discordant results were diagnosed with lymphoma, while 9/16 (56%) patients with discordant results had benign findings. CONCLUSION: With a diagnostic accuracy of 91%, FNA with cytology is sufficient to screen patients with indeterminate and incidental lymphadenopathy. Flow cytometry could be initially deferred in patients with low pretest probability of lymphoma.

Assessing PD-L1 Expression Status Using Radiomic Features from Contrast-Enhanced Breast MRI in Breast Cancer Patients: Initial Results.

The purpose of this retrospective study was to assess whether radiomics analysis coupled with machine learning (ML) based on standard-of-care dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict PD-L1 expression status in patients with triple negative breast cancer, and to compare the performance of this approach with radiologist review. Patients with biopsy-proven triple negative breast cancer who underwent pre-treatment breast MRI and whose PD-L1 status was available were included. Following 3D tumor segmentation and extraction of radiomic features, radiomic features with significant differences between PD-L1+ and PD-L1- patients were determined, and a final predictive model to predict PD-L1 status was developed using a coarse decision tree and five-fold cross-validation. Separately, all lesions were qualitatively assessed by two radiologists independently according to the BI-RADS lexicon. Of 62 women (mean age 47, range 31-81), 27 had PD-L1- tumors and 35 had PD-L1+ tumors. The final radiomics model to predict PD-L1 status utilized three MRI parameters, i.e., variance (FO), run length variance (RLM), and large zone low grey level emphasis (LZLGLE), for a sensitivity of 90.7%, specificity of 85.1%, and diagnostic accuracy of 88.2%. There were no significant associations between qualitative assessed DCE-MRI imaging features and PD-L1 status. Thus, radiomics analysis coupled with ML based on standard-of-care DCE-MRI is a promising approach to derive prognostic and predictive information and to select patients who could benefit from anti-PD-1/PD-L1 treatment.

AI-enhanced breast imaging: Where are we and where are we heading?

Significant advances in imaging analysis and the development of high-throughput methods that can extract and correlate multiple imaging parameters with different clinical outcomes have led to a new direction in medical research. Radiomics and artificial intelligence (AI) studies are rapidly evolving and have many potential applications in breast imaging, such as breast cancer risk prediction, lesion detection and classification, radiogenomics, and prediction of treatment response and clinical outcomes. AI has been applied to different breast imaging modalities, including mammography, ultrasound, and magnetic resonance imaging, in different clinical scenarios. The application of AI tools in breast imaging has an unprecedented opportunity to better derive clinical value from imaging data and reshape the way we care for our patients. The aim of this study is to review the current knowledge and future applications of AI-enhanced breast imaging in clinical practice.

Radiomics and Machine Learning with Multiparametric Breast MRI for Improved Diagnostic Accuracy in Breast Cancer Diagnosis.

The purpose of this multicenter retrospective study was to evaluate radiomics analysis coupled with machine learning (ML) of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) radiomics models separately and combined as multiparametric MRI for improved breast cancer detection. Consecutive patients (Memorial Sloan Kettering Cancer Center, January 2018-March 2020; Medical University Vienna, from January 2011-August 2014) with a suspicious enhancing breast tumor on breast MRI categorized as BI-RADS 4 and who subsequently underwent image-guided biopsy were included. In 93 patients (mean age: 49 years ± 12 years; 100% women), there were 104 lesions (mean size: 22.8 mm; range: 7-99 mm), 46 malignant and 58 benign. Radiomics features were calculated. Subsequently, the five most significant features were fitted into multivariable modeling to produce a robust ML model for discriminating between benign and malignant lesions. A medium Gaussian support vector machine (SVM) model with five-fold cross validation was developed for each modality. A model based on DWI-extracted features achieved an AUC of 0.79 (95% CI: 0.70-0.88), whereas a model based on DCE-extracted features yielded an AUC of 0.83 (95% CI: 0.75-0.91). A multiparametric radiomics model combining DCE- and DWI-extracted features showed the best AUC (0.85; 95% CI: 0.77-0.92) and diagnostic accuracy (81.7%; 95% CI: 73.0-88.6). In conclusion, radiomics analysis coupled with ML of multiparametric MRI allows an improved evaluation of suspicious enhancing breast tumors recommended for biopsy on clinical breast MRI, facilitating accurate breast cancer diagnosis while reducing unnecessary benign breast biopsies.

Multidimensional Diffusion Magnetic Resonance Imaging for Characterization of Tissue Microstructure in Breast Cancer Patients: A Prospective Pilot Study.

Diffusion-weighted imaging is a non-invasive functional imaging modality for breast tumor characterization through apparent diffusion coefficients. Yet, it has so far been unable to intuitively inform on tissue microstructure. In this IRB-approved prospective study, we applied novel multidimensional diffusion (MDD) encoding across 16 patients with suspected breast cancer to evaluate its potential for tissue characterization in the clinical setting. Data acquired via custom MDD sequences was processed using an algorithm estimating non-parametric diffusion tensor distributions. The statistical descriptors of these distributions allow us to quantify tissue composition in terms of metrics informing on cell densities, shapes, and orientations. Additionally, signal fractions from specific cell types, such as elongated cells (bin1), isotropic cells (bin2), and free water (bin3), were teased apart. Histogram analysis in cancers and healthy breast tissue showed that cancers exhibited lower mean values of "size" (1.43 ± 0.54 × 10-3 mm2/s) and higher mean values of "shape" (0.47 ± 0.15) corresponding to bin1, while FGT (fibroglandular breast tissue) presented higher mean values of "size" (2.33 ± 0.22 × 10-3 mm2/s) and lower mean values of "shape" (0.27 ± 0.11) corresponding to bin3 (p < 0.001). Invasive carcinomas showed significant differences in mean signal fractions from bin1 (0.64 ± 0.13 vs. 0.4 ± 0.25) and bin3 (0.18 ± 0.08 vs. 0.42 ± 0.21) compared to ductal carcinomas in situ (DCIS) and invasive carcinomas with associated DCIS (p = 0.03). MDD enabled qualitative and quantitative evaluation of the composition of breast cancers and healthy glands.

Diagnostic value of radiomics and machine learning with dynamic contrast-enhanced magnetic resonance imaging for patients with atypical ductal hyperplasia in predicting malignant upgrade.

PURPOSE: To investigate whether radiomics features extracted from magnetic resonance imaging (MRI) of patients with biopsy-proven atypical ductal hyperplasia (ADH) coupled with machine learning can differentiate high-risk lesions that will upgrade to malignancy at surgery from those that will not, and to determine if qualitatively and semi-quantitatively assessed imaging features, clinical factors, and image-guided biopsy technical factors are associated with upgrade rate. METHODS: This retrospective study included 127 patients with 139 breast lesions yielding ADH at biopsy who were assessed with multiparametric MRI prior to biopsy. Two radiologists assessed all lesions independently and with a third reader in consensus according to the BI-RADS lexicon. Univariate analysis and multivariate modeling were performed to identify significant radiomic features to be included in a machine learning model to discriminate between lesions that upgraded to malignancy on surgery from those that did not. RESULTS: Of 139 lesions, 28 were upgraded to malignancy at surgery, while 111 were not upgraded. Diagnostic accuracy was 53.6%, specificity 79.2%, and sensitivity 15.3% for the model developed from pre-contrast features, and 60.7%, 86%, and 22.8% for the model developed from delta radiomics datasets. No significant associations were found between any radiologist-assessed lesion parameters and upgrade status. There was a significant correlation between the number of specimens sampled during biopsy and upgrade status (p = 0.003). CONCLUSION: Radiomics analysis coupled with machine learning did not predict upgrade status of ADH. The only significant result from this analysis is between the number of specimens sampled during biopsy procedure and upgrade status at surgery.

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.

MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.

BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20). FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test). INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients. FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.