Apparent diffusion coefficient and intravoxel incoherent motion-derived true diffusion serve as early non-contrast longitudinal biomarkers of neoadjuvant chemotherapy response.

Locally advanced breast cancer (LABC) frequently requires neoadjuvant chemotherapy (NAC), and early, non-contrast imaging biomarkers are of increasing clinical interest for monitoring treatment response. Diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) MRI provide quantitative measures of tumour microstructure without gadolinium administration. To evaluate whether the apparent diffusion coefficient (ADC) and true diffusion (Dt) derived from IVIM can serve as early non-contrast imaging biomarkers of NAC response in patients with LABC. Fourteen women with biopsy-proven LABC underwent MRI at baseline (T0), after the first NAC cycle (T1), and after the third cycle (T2). ADC was calculated from b = 0 and 1000 s/mm², while Dt, Dp, and f were obtained using a full bi-exponential IVIM model incorporating all b-values (0-1000 s/mm²). Only four patients completed all three MRI timepoints. Tumour diameter and diffusion parameters were compared across time. At baseline, ADC and Dt were significantly lower in malignant lesions compared with contralateral fibroglandular tissue (p < 0.01). Following NAC, mean tumour ADC increased by 27.2% at T1 and 39.5% at T2, accompanied by progressive tumour size reduction (50.9% at T2). Dt demonstrated a similar upward trend. Perfusion-related IVIM parameters (Dp and f) showed no consistent differences. ROC analysis demonstrated high discriminatory performance of ADC for differentiating invasive ductal carcinoma from normal tissue (AUC = 1.00), although this finding must be interpreted cautiously given the small sample size. ADC and Dt showed early increases following NAC that paralleled reductions in tumour size, supporting their potential as practical, contrast-free imaging biomarkers of treatment-related microstructural changes. However, the limited number of complete longitudinal datasets (n = 4) and the pilot nature of the study require cautious interpretation. Larger prospective studies are needed to validate these findings.