Popis |
1. Introduction Over recent decades, the investigation of elemental, metallic, and protein distributions in biological tissues has gained prominence, especially within pharmaceutical and biomedical research [1-3]. This field has prioritized the development of targeted diagnostic and therapeutic interventions for cerebrovascular diseases, including ischemic stroke, a leading cause of mortality in developed nations. Given the critical need for early intervention, the study of novel drugs and their therapeutic impact is paramount. The combined use of computed tomography (CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) provides a powerful framework for evaluating the efficacy of stroke treatments (see Fig. 1). This dual-modality imaging approach not only enables high-resolution 3D visualization of pathological tissues but also allows for chemical analysis of specific brain structures, revealing progression markers such as hemorrhage, vessel recanalization, and clot dissolution rates. 2. Experimental setup LA-ICP-MS analysis - in this study, the distribution of key elements (P, Fe, Ba, I) was examined using an LAICP- MS system, specifically the LSX-213G2+ laser ablation platform (Teledyne, Photon Machines, USA) with a Q-Switch Nd laser at 213 nm. CT analysis - concurrently, samples were scanned via a GE phoenix v|tome|x L240 micro-CT system (Waygate Technologies) equipped with a high-resolution flat panel detector (4000 x 4000 pixels; 100 µm pixel size) and a nanofocus X-ray tube (100 kV, 250 µA) to capture detailed structural images. 3. Results and discussion Across 130 rat brain samples with varying degrees of stroke and drug dosages, combined CT and LA-ICP-MS analyses revealed distinct pathological markers. CT imaging highlighted regions of interest, such as white spots indicating potential hemorrhages, which were confirmed by increased iron concentrations via LA-ICP-MS (Fig. 2). Hematoxylin and eosin (HE) staining further validated these findings. The integration of LA-ICP-MS with CT facilitated the 3D segmentation of hemorrhagic regions (red in 3D model of brain) and enabled volumetric analysis of clots (yellow in 3D model of brain) within ischemic regions, demonstrating a gradual reduction in clot volume during treatment (means recanalization of the vessel of interest). 4. Conclusion 1) The results suggest that LA-ICP-MS holds significant potential as an innovative method for the detection, chemical characterization, and 2D imaging of pathological objects in biological samples (e.g. bleeding or level of clot dissolution). 2) Furthermore, when combined with CT techniques, it enables the acquisition of 3D images of these objects in biological tissues, along with segmentation and volumetric analysis to provide a comprehensive view of their distribution and effects on tissue alterations.
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