Illuminating the Brain With X-Rays: Contributions and Future Perspectives of High-Resolution Microtomography to Neuroscience

Rodrigues, Paulla Vieira; Tostes, Katiane; Bosque, Beatriz Pelegrini; Godoy, João Vitor Pereira de; Neto, Dionísio Pedro Amorim; Dias, Carlos Sato Baraldi; Fonseca, Matheus de Castro

doi:10.3389/fnins.2021.627994

Cited by 7 publications

(8 citation statements)

References 109 publications

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“…Micro-CT imaging, combined with the contrasting agents, achieves data similar to MRI, which is a long, expensive and intensive process. Micro-CT also delivers higher voxel diameter resolution and guarantees that the cerebral morphology remains intact for the construction of 3D models, with a high level of detail and resolution 58 . Comparing micro-CT and micro-MRI ex-vivo scans reported in the literature, the micro-CT scan of a brain takes around 5 h to complete, whereas micro-MRI takes up to 12 h, at an isotropic resolution of 62.5 µm 59 .…”

Section: Discussionmentioning

confidence: 99%

High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models

Pinto

Matula

Gómez-Lázaro

et al. 2022

Sci Rep

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Characterization of brain infarct lesions in rodent models of stroke is crucial to assess stroke pathophysiology and therapy outcome. Until recently, the analysis of brain lesions was performed using two techniques: (1) histological methods, such as TTC (Triphenyltetrazolium chloride), a time-consuming and inaccurate process; or (2) MRI imaging, a faster, 3D imaging method, that comes at a high cost. In the last decade, high-resolution micro-CT for 3D sample analysis turned into a simple, fast, and cheaper solution. Here, we successfully describe the application of brain contrasting agents (Osmium tetroxide and inorganic iodine) for high-resolution micro-CT imaging for fine location and quantification of ischemic lesion and edema in mouse preclinical stroke models. We used the intraluminal transient MCAO (Middle Cerebral Artery Occlusion) mouse stroke model to identify and quantify ischemic lesion and edema, and segment core and penumbra regions at different time points after ischemia, by manual and automatic methods. In the transient-ischemic-attack (TIA) mouse model, we can quantify striatal myelinated fibers degeneration. Of note, whole brain 3D reconstructions allow brain atlas co-registration, to identify the affected brain areas, and correlate them with functional impairment. This methodology proves to be a breakthrough in the field, by providing a precise and detailed assessment of stroke outcomes in preclinical animal studies.

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Section: Discussionmentioning

confidence: 99%

High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models

Pinto

Matula

Gómez-Lázaro

et al. 2022

Sci Rep

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“…Micro-CT imaging matched tissue contrast achieved by longer, more expensive, and step intensive MRI, while delivering higher voxel diameter resolution. Moreover, micro-CT guarantees that the cerebral morphology remains intact and allows the construction of 3D models with higher level of detail and resolution 61 . However, micro-CT investigation with this resolution in soft tissues can only be performed ex-vivo post-mortem, whereas MRI permits longitudinal assessment of lesion growth in the same individual.…”

Section: Discussionmentioning

confidence: 99%

High resolution micro-CT imaging in mice stroke models: from 3D detailed infarct characterization to automatic area segmentation

Pinto

Matula

Gómez-Lázaro

et al. 2022

Preprint

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Characterization of brain infarct lesion in rodent models of stroke is crucial to assess the outcome of stroke therapies and to study the disease pathophysiology. However, so far it has been mostly performed by: 1) histological methods, a time-consuming process that lead to significant flaws and tissue distortion; or 2) via MRI imaging, which is faster, yielding 3D information but at high costs. High-resolution micro-CT imaging became, in the last decade, a simple, fast, and cheaper solution, allowing 3D analysis of samples. Here, we describe that high-resolution micro-CT, either using iodine/OsO4 as contrast agents, can be successfully applied for fine quantification and localization of lesion size and edema volume in preclinical stroke models. We successfully correlated this new approach with the standard histological method TTC. In transient MCAO mouse stroke model, we were able to identify/quantify large lesioned areas (segmented in core and penumbra), up to degenerated finer striatal myelinated fibers in a transient ischemic attack (TIA) mouse model, at different timepoints post-ischemia, through manual and automatic segmentation approaches (deep learning). Furthermore, 3D reconstructions of the whole brain allow for brain atlas co-registration of the specific affected brain areas. Hence, the presented methodology, through iodine/OsO4 micro-CT imaging, constitutes a valuable advance in tools for precise and detailed assessment of stroke outcomes in preclinical animal studies.

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“…However, to obtain a high discriminative power, methods for enhancing the contrast between different tissue constituents are required. At present, the most promising contrast-enhancing methods include phase-contrast microCT (PCCT) ( Takeda et al, 2013 ; Barbone et al, 2021 ; Rodgers et al, 2021 , 2022 ; Chourrout et al, 2022a , b ; Palermo et al, 2022 ) and contrast-enhanced microCT (CECT) ( Rodrigues et al, 2021 ). While PCCT makes use of the refractive properties of the X-rays, CECT aims to increase the X-ray attenuating properties of different tissue constituents (e.g., white matter versus gray matter) by incubating or infiltrating the tissue with contrast-enhancing staining agents (CESAs).…”

Section: Introductionmentioning

confidence: 99%

Revealing the three-dimensional murine brain microstructure by contrast-enhanced computed tomography

Balcaen

Piens

Mwema³

et al. 2023

Front. Neurosci.

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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.

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Illuminating the Brain With X-Rays: Contributions and Future Perspectives of High-Resolution Microtomography to Neuroscience

Cited by 7 publications

References 109 publications

High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models

High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models

High resolution micro-CT imaging in mice stroke models: from 3D detailed infarct characterization to automatic area segmentation

Revealing the three-dimensional murine brain microstructure by contrast-enhanced computed tomography

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