Contrast Enhanced Spectral Mammography (CESM) is a dual-energy mammographic imaging technique that first requires intravenously administering an iodinated contrast medium. Then, it collects both a low-energy image, comparable to standard mammography, and a high-energy image. The two scans are combined to get a recombined image showing contrast enhancement. Despite CESM diagnostic advantages for breast cancer diagnosis, the use of contrast medium can cause side effects, and CESM also beams patients with a higher radiation dose compared to standard mammography. To address these limitations, this work proposes using deep generative models for virtual contrast enhancement on CESM, aiming to make CESM contrast-free and reduce the radiation dose. Our deep networks, consisting of an autoencoder and two Generative Adversarial Networks, the Pix2Pix, and the CycleGAN, generate synthetic recombined images solely from low-energy images. We perform an extensive quantitative and qualitative analysis of the model's performance, also exploiting radiologists' assessments, on a novel CESM dataset that includes 1138 images. As a further contribution to this work, we make the dataset publicly available. The results show that CycleGAN is the most promising deep network to generate synthetic recombined images, highlighting the potential of artificial intelligence techniques for virtual contrast enhancement in this field.

Objectives: To evaluate the correlation between radiomic features extracted from contrast-enhanced mammography (CEM) tumor lesions and peritumoral background with prognostic factors in breast cancer (BC). Methods: In this retrospective, single-center study, 134 women with histologically confirmed breast cancer underwent CEM examination. Radiomic features were extracted from manually segmented lesions and lesion contours were automatically delineated using PyRadiomics. The extracted features were categorized into seven classes: First-order Features, Shape Features (2D), Gray Level Co-occurrence Matrix (GLCM), Gray Level Run Length Matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), and Neighboring Gray Tone Difference Matrix (NGTDM). Histological examination assessed tumor type, grade, receptor structure (ER, PgR, HER2), Ki67 index, and lymph node involvement. Pearson correlation and multivariate regression were applied to evaluate associations between radiomic features and prognostic factors. Results: Significant correlations were found between First-order Features and prognostic factors such as ER, PgR, and Ki67 (p < 0.05). GLCM-based texture features showed strong associations with Ki67 and HER2 (p < 0.01). Radiomic features from peritumoral regions, especially shape and GLSZM metrics, were significantly correlated with Ki67 and lymph node involvement. Conclusions: Radiomic analysis of both tumor and peritumoral regions offers significant insights into BC prognosis. These findings support the integration of radiomics into personalized diagnostic and therapeutic strategies, potentially improving clinical decision making in BC management.

This study aims to propose a multimodal, multi-view deep learning approach for breast cancer virtual biopsy, a non-invasive classification of breast lesions as malignant or benign, by integrating Full-Field Digital Mammography (FFDM) and Contrast-Enhanced Spectral Mammography (CESM). The work addresses the critical challenge of missing CESM data by introducing generative artificial intelligence (AI) to synthesize CESM images when unavailable, ensuring the continuity of diagnostic workflows. The proposed method uses FFDM and CESM images in both craniocaudal (CC) and mediolateral oblique (MLO) views. When CESM is missing, a CycleGAN-based generative model produces synthetic CESM images from FFDM inputs. For classification, three convolutional neural networks (ResNet18, ResNet50, and VGG16) are employed, and a two-stage late fusion strategy integrates view-specific and modality-specific malignancy probabilities, weighted by Matthews Correlation Coefficient (MCC), into a final malignancy score. The system's robustness under varying degrees of missing CESM data is tested by incrementally replacing real CESM inputs with synthetic ones and evaluating classification performance using AUC, G-mean, and MCC. CycleGAN achieved high-fidelity CESM synthesis, with Peak-Signal-to-Noise Ratio exceeding 24 dB and Structural Similarity Index above 0.8 across both CC and MLO views. For lesion classification, the multimodal configuration combining FFDM and CESM consistently outperformed the unimodal FFDM-only setup. Notably, even when CESM was entirely replaced by synthetic images, the multimodal approach still improved virtual biopsy performance compared to FFDM alone. Although classification performance declined as the proportion of synthetic CESM increased, the use of synthetic data remained beneficial. This work demonstrates that generative AI can effectively address missing-modality challenges in breast cancer diagnostics by synthesizing CESM images to enhance FFDM-based virtual biopsy pipelines. In the absence of real CESM data, incorporating synthetic images improves lesion classification compared to using FFDM alone, offering a non-invasive alternative to support clinical decision-making. Moreover, by releasing the extended CESM@UCBM dataset, this study contributes a valuable resource for advancing research and innovation in breast multimodal diagnostic systems.

Deep learning has revolutionized biomedical research by providing sophisticated methods to handle complex, high-dimensional data. Multimodal deep learning (MDL) further enhances this capability by integrating diverse data types such as imaging, textual data, and genetic information, leading to more robust and accurate predictive models. In MDL, differently from early and late fusion methods, intermediate fusion stands out for its ability to effectively combine modality-specific features during the learning process. This systematic review aims to comprehensively analyze and formalize current intermediate fusion methods in biomedical applications. We investigate the techniques employed, the challenges faced, and potential future directions for advancing intermediate fusion methods. Additionally, we introduce a structured notation to enhance the understanding and application of these methods beyond the biomedical domain. Our findings are intended to support researchers, healthcare professionals, and the broader deep learning community in developing more sophisticated and insightful multimodal models. Through this review, we aim to provide a foundational framework for future research and practical applications in the dynamic field of MDL.

Contrast-Enhanced Spectral Mammography (CESM) is a dual-energy mammographic technique that improves lesion visibility through the administration of an iodinated contrast agent. It acquires both a low-energy image, comparable to standard mammography, and a high-energy image, which are then combined to produce a dual-energy subtracted image highlighting lesion contrast enhancement. While CESM offers superior diagnostic accuracy compared to standard mammography, its use entails higher radiation exposure and potential side effects associated with the contrast medium. To address these limitations, we propose Seg-CycleGAN, a generative deep learning framework for Virtual Contrast Enhancement in CESM. The model synthesizes high-fidelity dual-energy subtracted images from low-energy images, leveraging lesion segmentation maps to guide the generative process and improve lesion reconstruction. Building upon the standard CycleGAN architecture, Seg-CycleGAN introduces localized loss terms focused on lesion areas, enhancing the synthesis of diagnostically relevant regions. Experiments on the CESM@UCBM dataset demonstrate that Seg-CycleGAN outperforms the baseline in terms of PSNR and SSIM, while maintaining competitive MSE and VIF. Qualitative evaluations further confirm improved lesion fidelity in the generated images. These results suggest that segmentation-aware generative models offer a viable pathway toward contrast-free CESM alternatives.

Contrast Enhanced Spectral Mammography (CESM) is a dual-energy mammographic imaging technique that first needs intravenously administration of an iodinated contrast medium; then, it collects both a low-energy image, comparable to standard mammography, and a high-energy image. The two scans are then combined to get a recombined image showing contrast enhancement. Despite CESM diagnostic advantages for breast cancer diagnosis, the use of contrast medium can cause side effects, and CESM also beams patients with a higher radiation dose compared to standard mammography. To address these limitations this work proposes to use deep generative models for virtual contrast enhancement on CESM, aiming to make the CESM contrast-free as well as to reduce the radiation dose. Our deep networks, consisting of an autoencoder and two Generative Adversarial Networks, the Pix2Pix, and the CycleGAN, generate synthetic recombined images solely from low-energy images. We perform an extensive quantitative and qualitative analysis of the model's performance, also exploiting radiologists' assessments, on a novel CESM dataset that includes 1138 images that, as a further contribution of this work, we make publicly available. The results show that CycleGAN is the most promising deep network to generate synthetic recombined images, highlighting the potential of artificial intelligence techniques for virtual contrast enhancement in this field.