Summary Intracerebral haemorrhage accounts for about 10–15% of all strokes and is associated with high mortality and morbidity. No successful phase 3 clinical trials for this disorder have been completed. In the past 6 years, the number of preclinical and clinical studies focused on intracerebral haemorrhage has risen. Important advances have been made in animal models of this disorder and in our understanding of mechanisms underlying brain injury after haemorrhage. Several therapeutic targets have subsequently been identified that are now being pursued in clinical trials. Many clinical trials have been based on limited preclinical data, and guidelines to justify taking preclinical results to the clinic are needed.

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Intracerebral haemorrhage: mechanisms of injury and therapeutic targets

Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation.

Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

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Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and morbidity. When a diseased artery within the brain bursts, expansion and absorption of the resulting hematoma trigger a series of reactions that cause primary and secondary brain injury. Microglia are extremely important for removing the hematoma and clearing debris, but they are also a source of ongoing inflammation. This article discusses the role of microglial activation/polarization and related inflammatory mediators, such as Toll-like receptor 4, matrix metalloproteinases, high-mobility group protein box-1, nuclear factor erythroid 2-related factor 2, heme oxygenase, and iron, in secondary injury after ICH and highlights the potential targets for ICH treatment.

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Microglial Polarization and Inflammatory Mediators After Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a leading cause of morbidity and mortality around the world. Currently, there is no effective medical treatment available to improve functional outcomes in patients with ICH due to its unknown mechanisms of damage. Increasing evidence has shown that the metabolic products of erythrocytes are the key contributor of ICH-induced secondary brain injury. Iron, an important metabolic product that accumulates in the brain parenchyma, has a detrimental effect on secondary injury following ICH. Because the damage mechanism of iron during ICH-induced secondary injury is clear, iron removal therapy research on animal models is effective. Although many animal and clinical studies have been conducted, the exact metabolic pathways of iron and the mechanisms of iron removal treatments are still not clear. This review summarizes recent progress concerning the iron metabolism mechanisms underlying ICH-induced injury. We focus on iron, brain iron metabolism, the role of iron in oxidative injury, and iron removal therapy following ICH, and we suggest that further studies focus on brain iron metabolism after ICH and the mechanism for iron removal therapy.

Iron and Intracerebral Hemorrhage: From Mechanism to Translation

Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome.

A median-Gaussian filtering framework for Moiré pattern noise removal from X-ray microscopy image.

We describe a spectral x-ray transmission method to provide images of independent material components of an object using a synchrotron x-ray source. The imaging system and process is similar to K-edge subtraction (KES) imaging where two imaging energies are prepared above and below the K-absorption edge of a contrast element and a quantifiable image of the contrast element and a water equivalent image are obtained. The spectral method, termed 'spectral-KES' employs a continuous spectrum encompassing an absorption edge of an element within the object. The spectrum is prepared by a bent Laue monochromator with good focal and energy dispersive properties. The monochromator focuses the spectral beam at the object location, which then diverges onto an area detector such that one dimension in the detector is an energy axis. A least-squares method is used to interpret the transmitted spectral data with fits to either measured and/or calculated absorption of the contrast and matrix material-water. The spectral-KES system is very simple to implement and is comprised of a bent Laue monochromator, a stage for sample manipulation for projection and computed tomography imaging, and a pixelated area detector. The imaging system and examples of its applications to biological imaging are presented. The system is particularly well suited for a synchrotron bend magnet beamline with white beam access.

https://iopscience.iop.org/article/10.1088/0031-9155/59/10/2485/pdf

Spectral K-edge subtraction imaging.

Ring artifacts can occur in reconstructed images from x-ray Computerized Tomography (CT) as full or partial concentric rings superimposed on the scanned structures. Due to the data corruption by those ring artifacts in CT images, qualitative and quantitative analysis of these images are compromised. In this paper, we propose to correct the ring artifacts on the reconstructed synchrotron radiation (SR) CT image slices. The proposed correction procedure includes the following steps: (1). transform the reconstructed CT images into polar coordinates; (2) apply discrete two-dimensional (2D) wavelet transform to the polar image to decompose it into four image components: low pass band image component, as well as the components from horizontal, vertical and diagonal details bands; (3). apply 2D Fourier transform to the vertical details band image component only, since the ring artifacts become vertical lines in the polar coordinates; (4). apply Gaussian filtering in Fourier domain along the abscissa direction to suppress the vertical lines, since the information of the vertical lines in Fourier domain is completely condensed to that direction; (5). perform inverse Fourier transform to get the corrected vertical details band image component; (6). perform inverse wavelet transform to get the corrected polar image; (7). transform the corrected polar image back to Cartesian coordinates to get the CT image slice with reduced ring artifacts. This approach has been successfully used on CT data acquired from the Biomedical Imaging and Therapy (BMIT) beamline in Canadian Light Source (CLS), and the results show that the ring artifacts in original SR CT images have been effectively suppressed with all the structure information in the image preserved.

https://iopscience.iop.org/article/10.1088/1748-0221/8/06/C06006/pdf

Ring artifacts removal from synchrotron CT image slices

Refraction x-ray contrast is an imaging modality used primarily in a research setting at synchrotron facilities, which have a biomedical imaging research program. The most common method for exploiting refraction contrast is by using a technique called Diffraction Enhanced Imaging (DEI). The DEI apparatus allows the detection of refraction between two materials and produces a unique ''edge enhanced'' contrast appearance, very different from the traditional absorption x-ray imaging used in clinical radiology. In this paper we aim to explain the features of x-ray refraction contrast as a typical clinical radiologist would understand. Then a discussion regarding what needs to be considered in the interpretation of the refraction image takes place. Finally we present a discussion about the limitations of planar refraction imaging and the potential of DEI Computed Tomography. This is an original work that has not been submitted to any other source for publication. The authors have no commercial interests or conflicts of interest to disclose.

http://iopscience.iop.org/article/10.1088/1748-0221/8/05/C05004/pdf

Zhouping Wei

Papers

Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome.

A median-Gaussian filtering framework for Moiré pattern noise removal from X-ray microscopy image.

Spectral K-edge subtraction imaging.

Ring artifacts removal from synchrotron CT image slices

Understanding refraction contrast using a comparison of absorption and refraction computed tomographic techniques