Читать книгу Magnetic Resonance Microscopy - Группа авторов - Страница 22

Brain-implanted microelectrodes target devastating diseases such as Parkinsons or epilepsy, and one of the primary questions in the field is whether it is possible to use noninvasive MRI to diagnose the disease, monitor recovery and temporal evolution of disease progress, and confirm correct system function of the implant. The hope is to translate diagnostic findings from mouse models to humans, despite certain differences, but with the benefit of using higher fields and hence higher-resolution techniques on model organisms than are generally available for humans. The gold standard for epileptogenesis is a kainate-initiated temporal lobe epilepsy mouse model established by Bouilleret et al. [40], for which a dedicated MR-compatible tissue slice environment was developed [35]. In this device, a freshly extracted brain slice 5 mm diameter, 500 µm thickness is maintained at physiological conditions (36°C, perfused, oxygenated) during MRI (Figure 1.7). Additional studies, which tracked the morphological changes of the brain slice over longer timeframes, were performed using a cryogenic vendor-supplied small animal coil [41], for the first time yielding confirmation of histological correlates with various MRI modalities. Using the same cryo-imaging coil, translation of these techniques to the full animal model yielded a comprehensive picture of the disease progression [42] and established a number of new measurement and postprocessing techniques, including high-resolution diffusion tensor imaging, see Figures 1.9 and 1.10.

Figure 1.9 Magnetic resonance (MR) and histological images of fixed hippocampal sections of two control animals (Section 1: A–D, with an adjacent section used for Golgi staining: E; Section 2: F–I). (A, B, F, G) Structural magnetic resonance imaging (MRI) depicts the main neuronal cell layers and tissue architecture. Comparison of diffusion tractography images (C, H) to corresponding NeuN and ZnT3 immunostaining (D, I) shows that regions containing parallel extending dendrites of principal neurons evoke corresponding diffusion-weighted imaging (DWI) streamlines. (E) Golgi staining of an adjacent section depicts the localization and orientation of principal cell dendrites (blue arrowheads in SR and ML) and parts of mossy fibers in CA3 (red arrowheads). (J) DiI crystal placed into the CA1 stratum radiatum, showing the orientation of CA1 pyramidal cells as well as of innervating CA3 Schaffer collaterals (asterisk and arrowheads, respectively). Scale bar: 500 µm. [41] Katharina Göbel-Guéniot et al. (2020), figure 02[p.06]/Frontiers Media S.A./CC BY 4.0.

Figure 1.10 Microstructural reorganization quantified by diffusion-weighted imaging (DWI) during epileptogenesis predicts disease progression. (A1–6) Representative coronal sections from diffusion-weighted tractography at different time points during epileptogenesis (before injection = pre; 1 day, 4 days, 7 days, 14 days, and 31 days following SE). (B1–6) Enlarged images. (C–D) Representative tractography image and a Nissl-stained section of corresponding brain regions for anatomical comparison. Computed fibers relate to major axonal pathways and brain regions exhibiting highly oriented dendrites (cc, corpus callosum). (E, G) Enlarged tractography images demonstrating the distinct orientation of streamlines in different hippocampal layers. (F, H) Corresponding 4′,6-diamidino-2-phenylindole (DAPI)-stained sections. Scale bars in A, 2 mm; B–D, 500 mm; H (left), 100 mm (I, K, M, O). Quantitative analysis of DWI metrics in the dentate gyrus (DG), plotted for individual mice (left panel; controls, black, n = 5; kainate-injected animals color-coded) and for groups during epileptogenesis. [42] Philipp Janz et al. (2017), figure 05[p.10]/eLife Sciences Publications Ltd./CC BY 4.0.