Balcaen Tim, Piens Catherine, Mwema Ariane, Chourrout Matthieu, Vandebroek Laurens, Des Rieux Anne, Chauveau Fabien, De Borggraeve Wim M, Hoffmann Delia, Kerckhofs Greet
MolDesignS, Sustainable Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Leuven, Belgium.
ContrasT Team, Institute of Mechanics, Materials and Civil Engineering, Mechatronic, Electrical Energy and Dynamic Systems, UCLouvain, Louvain-la-Neuve, Belgium.
Front Neurosci. 2023 Mar 23;17:1141615. doi: 10.3389/fnins.2023.1141615. eCollection 2023.
To improve our understanding of the brain microstructure, high-resolution 3D imaging is used to complement classical 2D histological assessment techniques. X-ray computed tomography allows high-resolution 3D imaging, but requires methods for enhancing contrast of soft tissues. Applying contrast-enhancing staining agents (CESAs) ameliorates the X-ray attenuating properties of soft tissue constituents and is referred to as contrast-enhanced computed tomography (CECT). Despite the large number of chemical compounds that have successfully been applied as CESAs for imaging brain, they are often toxic for the researcher, destructive for the tissue and without proper characterization of affinity mechanisms. We evaluated two sets of chemically related CESAs (organic, iodinated: Hexabrix and CA4+ and inorganic polyoxometalates: 1:2 hafnium-substituted Wells-Dawson phosphotungstate and Preyssler anion), for CECT imaging of healthy murine hemispheres. We then selected the CESA (Hexabrix) that provided the highest contrast between gray and white matter and applied it to a cuprizone-induced demyelination model. Differences in the penetration rate, effect on tissue integrity and affinity for tissue constituents have been observed for the evaluated CESAs. Cuprizone-induced demyelination could be visualized and quantified after Hexabrix staining. Four new non-toxic and non-destructive CESAs to the field of brain CECT imaging were introduced. The added value of CECT was shown by successfully applying it to a cuprizone-induced demyelination model. This research will prove to be crucial for further development of CESAs for ex vivo brain CECT and 3D histopathology.
为了增进我们对脑微观结构的理解，高分辨率三维成像被用于补充传统的二维组织学评估技术。X射线计算机断层扫描能够实现高分辨率三维成像，但需要增强软组织对比度的方法。应用造影增强染色剂（CESAs）可改善软组织成分的X射线衰减特性，这被称为造影增强计算机断层扫描（CECT）。尽管有大量化合物已成功用作脑成像的CESAs，但它们往往对研究人员有毒，对组织有破坏性，且缺乏对亲和机制的恰当表征。我们评估了两组化学相关的CESAs（有机碘化剂：Hexabrix和CA4 +以及无机多金属氧酸盐：1:2铪取代的韦尔斯-道森磷钨酸盐和普雷伊斯勒阴离子），用于健康小鼠半球的CECT成像。然后，我们选择了在灰质和白质之间提供最高对比度的CESA（Hexabrix），并将其应用于铜螯合剂诱导的脱髓鞘模型。对于所评估的CESAs，观察到了其在渗透率、对组织完整性的影响以及对组织成分的亲和力方面的差异。在Hexabrix染色后，铜螯合剂诱导的脱髓鞘能够被可视化和量化。引入了四种用于脑CECT成像领域的新型无毒且非破坏性的CESAs。通过将CECT成功应用于铜螯合剂诱导的脱髓鞘模型，展示了其附加价值。这项研究对于用于离体脑CECT和三维组织病理学的CESAs的进一步发展将被证明至关重要。
