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

<b>Background:</b> 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. <b>Methods:</b> BALB/c mice with 4T1 tumors (<i>n</i> = 30) were randomized into PTT or control groups. Serial MRI (0.5-24 h post-PTT) quantified intravoxel incoherent motion (IVIM: <i>D</i>, <i>D</i>*, <i>f</i>) and blood oxygenation level-dependent (BOLD: <i>R</i>2*) parameters, validated by fiber-optic pH telemetry and immunohistochemistry (<i>K</i> _i-67, HIF-1α, TUNEL). <b>Results:</b> PTT induced significant spatiotemporal changes in both imaging biomarkers and pathological indicators. IVIM analysis revealed: (1) Biphasic <i>D</i>-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*/<i>f</i> increase at 0.5 h) followed by progressive microcirculation suppression. BOLD MRI demonstrated progressive <i>R</i>2* reduction, reaching maximum decrease at 24 h (<i>p</i> < 0.001), paralleled by significant tumor alkalinization (pH increase, <i>p</i> < 0.05). Histopathological correlations showed: (1) Strong inverse associations between <i>R</i>2* and both <i>K</i> _i-67 (<i>r</i> = -0.733, <i>p</i> < 0.001) and HIF-1α (<i>r</i> = -0.777, <i>p</i> < 0.001); (2) Positive perfusion-apoptosis correlations (<i>f</i> vs TUNEL: <i>r</i> = 0.595, <i>p</i> = 0.003); (3) Delayed <i>D</i>-value/<i>K</i> _i-67 negative correlation at later time points (<i>r</i> = 0.7609, <i>P</i> = 0.0065). <b>Conclusion:</b> Multiparametric MRI delineates PTT-induced TME reprogramming, with IVIM (<i>D</i>*, <i>f</i>) predicting acute vascular modulation and BOLD (<i>R</i>2*) tracking hypoxia alleviation. This framework enables real-time therapy guidance and early efficacy assessment.