Mapping the Intratumoral and Peritumoral Microenvironment: Multilayered Shell ADC Analysis and Its Association with...

Objective: This study aimed to investigate the associations between intratumoral and peritumoral apparent diffusion coefficient (ADC) measurements and multiparametric biological markers in invasive breast cancer using a novel peritumoral analysis approach. Materials and Methods: In this retrospective study, 68 patients underwent 1.5 T breast magnetic resonance imaging. Following volumetric tumor segmentation, the peritumoral environment was analyzed using a segmentation-based, improved multilayered concentric shell model at distances of 0-2, 2-5, and 5-10 mm. The ADC values were normalized to contralateral parenchyma (rADC), and the intratumoral-to-peritumoral ADC ratios were calculated. Parameters were correlated with molecular subtypes, axillary metastasis, lymphovascular invasion (LVI), histologic grade, and Ki-67 index. Results: Lower intratumoral ADC and lower intratumoral-to-peritumoral ADC ratios were significantly associated with higher histologic grade, increased Ki-67, and axillary metastasis (p < 0.05). The 0-2 mm shell, representing the immediate invasion front, demonstrated the strongest associations with lymphovascular invasion and nodal involvement, while distance-dependent attenuation of effect sizes was observed across more distal peritumoral layers. Conclusions: The segmentation-based and improved multilayered shell model effectively captures the distance-dependent biological gradient of the peritumoral microenvironment. The intratumoral-to-peritumoral ADC ratios within the immediate 2 mm zone may provide complementary information regarding imaging markers of tumor aggressiveness when interpreted alongside absolute measurements. These findings suggest a potential role for these parameters as complementary imaging markers in preoperative risk stratification within a multiparametric framework.