Spatiotemporal Mapping of Tumor Microenvironment Remodeling During Fiber-Optic Photothermal Therapy: A Multiparametric MRI Study in 4T1 Breast Cancer Xenografts.

Background: Photothermal therapy (PTT) mediated by fiber-optic technology shows promise for breast cancer treatment, but its acute effects on the tumor microenvironment (TME) remain poorly characterized. This study integrates multiparametric MRI and fiber-optic biosensing to map early TME remodeling in 4T1 triple-negative breast cancer xenografts. Methods: BALB/c mice with 4T1 tumors (n = 30) were randomized into PTT or control groups. Serial MRI (0.5-24 h post-PTT) quantified intravoxel incoherent motion (IVIM: D, D*, f) and blood oxygenation level-dependent (BOLD: R2*) parameters, validated by fiber-optic pH telemetry and immunohistochemistry (K i-67, HIF-1α, TUNEL). Results: PTT induced significant spatiotemporal changes in both imaging biomarkers and pathological indicators. IVIM analysis revealed: (1) Biphasic D-value fluctuations in central/peripheral regions (initial increase at 0.5-2 h, decline at 4 h, recovery at 24 h); (2) Transient perfusion elevation (D*/f increase at 0.5 h) followed by progressive microcirculation suppression. BOLD MRI demonstrated progressive R2* reduction, reaching maximum decrease at 24 h (p < 0.001), paralleled by significant tumor alkalinization (pH increase, p < 0.05). Histopathological correlations showed: (1) Strong inverse associations between R2* and both K i-67 (r = -0.733, p < 0.001) and HIF-1α (r = -0.777, p < 0.001); (2) Positive perfusion-apoptosis correlations (f vs TUNEL: r = 0.595, p = 0.003); (3) Delayed D-value/K i-67 negative correlation at later time points (r = 0.7609, P = 0.0065). Conclusion: Multiparametric MRI delineates PTT-induced TME reprogramming, with IVIM (D*, f) predicting acute vascular modulation and BOLD (R2*) tracking hypoxia alleviation. This framework enables real-time therapy guidance and early efficacy assessment.