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中国物理学会期刊

基于刚性诱导长寿命三重态亚甲基蓝的高特异性光声泵浦成像

Highly Specific Pump-Probe Photoacoustic Tomography Based on Rigidity-Induced Long-Lived Triplet State Methylene Blue

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  • 相对于传统的光声成像,光声泵浦成像可以通过光敏剂分子的瞬态吸收效应,有效的排除组织中血液等强内源性吸收物质的影响,实现目标分子的有效探测。然而,现有的光声泵浦成像多基于亚甲基蓝(Methylene Blue,MB)等短三重态寿命光敏分子,只能采用相对较低的泵浦-探测延迟。由于泵浦光格鲁尼森效应的影响,强吸收背景组织也会产生微小的瞬态热弛豫差分信号,限制了其成像特异性的提高。为此,本文基于高分子刚性限域效应,通过固相聚乙烯醇的致密氢键网络有效抑制了MB分子的非辐射弛豫,成功延长了其三重态寿命,并在此基础上展开光声泵浦成像研究。结果表明,相比于传统的游离MB,经过该固相微环境调制的MB光敏剂分子可以使得光声泵浦成像的最优泵浦-探测延迟时间提高4.17倍,从而在相当的吸收水平条件下,使光声泵浦成像的特异性提高2.99倍。本研究揭示了光敏剂微环境刚性调控对光声泵浦成像的影响,对高特异性光声泵浦成像方法的开发具有重要的指导意义。

     

    As an upgrade to conventional photoacoustic tomography (PAT), pump-probe PAT (PP-PAT) exploits the transient excited-state absorption of photosensitizers to effectively eliminate interference from strong endogenous absorbers such as blood, enabling the accurate detection of target molecules. However, current PP-PAT techniques predominantly rely on photosensitizers with short triplet-state lifetimes, such as methylene blue (MB), restricting PP-PAT systems to relatively short pump-probe delay windows. Due to the Grüneisen relaxation effect, strongly absorbing background tissues can also generate weak, transient thermally induced photoacoustic signals that overlap within this narrow window, introducing artifacts and limiting molecular imaging specificity. To address this issue, we propose a physical strategy using a solid-state polyvinyl alcohol (PVA) matrix with high degrees of alcoholysis. PVA's dense 3D hydrogen-bonding network spatially confines MB molecules, suppressing non-radiative relaxation and extending their triplet-state lifetime for background-suppressed PP-PAT. Transient triplet differential (TTD) characterization and imaging were performed on free MB, PVA-MB composite films (~200 μm thick), pure hemoglobin (Hb), and Hb-MB mixtures using UV-Vis spectroscopy, fluorescence spectroscopy, and a PP-PAT system. Results show that the PVA matrix significantly prolonged the triplet lifetime of MB while preserving its ground-state absorption and excited-state transition absorption characteristics. As PVA alcoholysis increased (74.5%, 88%, and 99%), the triplet lifetime rose from 13.73 μs to 17.70 μs and 63.26 μs, respectively—over 40-fold longer than in pure water (1.57 μs). Compared to free MB, this solid-state microenvironment increased the optimal pump-probe delay by a factor of 4.17, achieving a 2.99-fold improvement in PP-PAT specificity under equivalent absorption conditions. This study elucidates how microenvironmental rigidity regulates photosensitizer behavior in PP-PAT, offering valuable guidance for developing highly specific PP-PAT approaches.

     

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