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

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide 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: R 2*) 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 R 2* 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 R 2* 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 ( R 2*) tracking hypoxia alleviation. This framework enables real-time therapy guidance and early efficacy assessment.

Source: Chemical & Biomedical Imaging

DOI: 10.1021/cbmi.5c00134