Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.

Intratumor heterogeneity (ITH) profoundly affects therapeutic responses and clinical outcomes. However, the widespread methods for assessing ITH based on genomic sequencing or pathological slides, which rely on limited tissue samples, may lead to inaccuracies due to potential sampling biases. Using a newly established multicenter breast cancer radio-multiomic dataset (n = 1474) encompassing radiomic features extracted from dynamic contrast-enhanced magnetic resonance images, we formulated a noninvasive radiomics methodology to effectively investigate ITH. Imaging ITH (IITH) was associated with genomic and pathological ITH, predicting poor prognosis independently in breast cancer. Through multiomic analysis, we identified activated oncogenic pathways and metabolic dysregulation in high-IITH tumors. Integrated metabolomic and transcriptomic analyses highlighted ferroptosis as a vulnerability and potential therapeutic target of high-IITH tumors. Collectively, this work emphasizes the superiority of radiomics in capturing ITH. Furthermore, we provide insights into the biological basis of IITH and propose therapeutic targets for breast cancers with elevated IITH.

Multiparameter MRI Model With DCE-MRI, DWI, and Synthetic MRI Improves the Diagnostic Performance of BI-RADS 4 Lesions.

OBJECTIVES: To evaluate the value of synthetic magnetic resonance imaging (syMRI), diffusion-weighted imaging (DWI), DCE-MRI, and clinical features in breast imaging-reporting and data system (BI-RADS) 4 lesions, and develop an efficient method to help patients avoid unnecessary biopsy. METHODS: A total of 75 patients with breast diseases classified as BI-RADS 4 (45 with malignant lesions and 30 with benign lesions) were prospectively enrolled in this study. T1-weighted imaging (T1WI), T2WI, DWI, and syMRI were performed at 3.0 T. Relaxation time (T1 and T2), apparent diffusion coefficient (ADC), conventional MRI features, and clinical features were assessed. "T" represents the relaxation time value of the region of interest pre-contrast scanning, and "T+" represents the value post-contrast scanning. The rate of change in the T value between pre- and post-contrast scanning was represented by ΔT%. RESULTS: ΔT1%, T2, ADC, age, body mass index (BMI), menopause, irregular margins, and heterogeneous internal enhancement pattern were significantly associated with a breast cancer diagnosis in the multivariable logistic regression analysis. Based on the above parameters, four models were established: model 1 (BI-RADS model, including all conventional MRI features recommended by BI-RADS lexicon), model 2 (relaxation time model, including ΔT1% and T2), model 3 [multi-parameter (mp)MRI model, including ΔT1%, T2, ADC, margin, and internal enhancement pattern], and model 4 (combined image and clinical model, including ΔT1%, T2, ADC, margin, internal enhancement pattern, age, BMI, and menopausal state). Among these, model 4 has the best diagnostic performance, followed by models 3, 2, and 1. CONCLUSIONS: The mpMRI model with DCE-MRI, DWI, and syMRI is a robust tool for evaluating the malignancies in BI-RADS 4 lesions. The clinical features could further improve the diagnostic performance of the model.