Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.
Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.
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DOI：
10.1016/j.biomaterials.2016.10.043
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发表时间：
2017-01
期刊：
影响因子：
14
通讯作者：
Modo M
中科院分区：
文献类型：
--
作者：
Jin T;Nicholls FJ;Crum WR;Ghuman H;Badylak SF;Modo M
细胞外基质（Extracellular matrix， ECM）作为一种诱导性生物支架被广泛应用于软组织损伤后的修复，其作用是促进植入材料的功能位点重构。然而，缺乏无创分析方法来监测植入后ECM材料的重塑特征及其随时间的生物降解。我们描述了使用抗磁性化学交换饱和转移（CEST）磁共振成像来监测脑内植入脑卒中腔后ECM水凝胶的分布。体外成像显示，ECM前体和水凝胶在1.8和3.6 ppm时具有很强的浓度依赖性检测，这与硫酸软骨素和纤维连接蛋白大致对应。这种检测对pH值的变化是稳健的，并且在37°C时得到改善。在大鼠脑卒中模型中植入ECM水凝胶，在宏观上与组织学上的生物材料分布一致，但也存在明显的不匹配。确实，CEST成像检测到内源性“沉积增加”。为了解释这种内源性活性，将植入前的图像从植入后的图像中减去，以获得脑卒中腔中水凝胶分布及其在7天内演变的选择性可视化。由于水凝胶中纤维连接蛋白和硫酸软骨素的减少，ECM的CEST检测在3天内恢复到基线。因此，ECM水凝胶在脑卒中腔内的分布在体内是可行的，但在生物降解的背景下，需要进一步的进展来保证选择性的长期监测。
Extracellular matrix (ECM) is widely used as an inductive biological scaffold to repair soft tissue after injury by promoting functional site-appropriate remodeling of the implanted material. However, there is a lack of non-invasive analysis methods to monitor the remodeling characteristics of the ECM material after implantation and its biodegradation over time. We describe the use of diamagnetic chemical exchange saturation transfer (CEST) magnetic resonance imaging to monitor the distribution of an ECM hydrogel after intracerebral implantation into a stroke cavity. In vitro imaging indicated a robust concentration-dependent detection of the ECM precursor and hydrogel at 1.8 and 3.6 ppm, which broadly corresponded to chondroitin sulfate and fibronectin. This detection was robust to changes in pH and improved at 37 °C. In vivo implantation of ECM hydrogel into the stroke cavity in a rat model corresponded macroscopically to the distribution of biomaterial as indicated by histology, but mismatches were also evident. Indeed, CEST imaging detected an endogenous “increased deposition”. To account for this endogenous activity, pre-implantation images were subtracted from post-implantation images to yield a selective visualization of hydrogel distribution in the stroke cavity and its evolution over 7 days. The CEST detection of ECM returned to baseline within 3 days due to a decrease in fibronectin and chondroitin sulfate in the hydrogel. The distribution of ECM hydrogel within the stroke cavity is hence feasible in vivo, but further advances are required to warrant a selective long-term monitoring in the context of biodegradation.
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