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Brain tissue iron quantification by MRI in intracerebral hemorrhage: Current translational evidence and pitfalls.

ABSTRACT: Intracerebral hemorrhage (ICH) is a common subtype of hemorrhagic stroke with devastating consequences with no specific treatment. There is, however, substantial evidence for iron-mediated neurotoxicity in animal ICH models. Non-invasive quantification of the peri-hematomal tissue iron based on MRI has shown some promise in animal models and is being validated for clinical translation. This commentary reviews evidence for this approach and discusses potential pitfalls.

SUBMITTER: Chaudhary N

PROVIDER: S-EPMC6421244 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Brain tissue iron quantification by MRI in intracerebral hemorrhage: Current translational evidence and pitfalls.

Chaudhary Neeraj N Pandey Aditya S AS Griauzde Julius J Gemmete Joseph J JJ Chenevert Thomas L TL Keep Richard F RF Xi Guohua G

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20181212 3

Intracerebral hemorrhage (ICH) is a common subtype of hemorrhagic stroke with devastating consequences with no specific treatment. There is, however, substantial evidence for iron-mediated neurotoxicity in animal ICH models. Non-invasive quantification of the peri-hematomal tissue iron based on MRI has shown some promise in animal models and is being validated for clinical translation. This commentary reviews evidence for this approach and discusses potential pitfalls. ...[more]

PMID: 30540218

Similar Datasets

Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

Project description:BACKGROUND AND PURPOSE:Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. METHODS:Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. RESULTS:ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits (P<0.05). CONCLUSIONS:Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats.

| S-EPMC5871578 | biostudies-literature

Preclinical Studies and Translational Applications of Intracerebral Hemorrhage.

Project description:Intracerebral hemorrhage (ICH) which refers to bleeding in the brain is a very deleterious condition with high mortality and disability rate. Surgery or conservative therapy remains the treatment option. Various studies have divided the disease process of ICH into primary and secondary injury, for which knowledge into these processes has yielded many preclinical and clinical treatment options. The aim of this review is to highlight some of the new experimental drugs as well as other treatment options like stem cell therapy, rehabilitation, and nanomedicine and mention some translational clinical applications that have been done with these treatment options.

| S-EPMC5494071 | biostudies-literature

White Matter Survival within and around the Hematoma: Quantification by MRI in Patients with Intracerebral Hemorrhage.

Project description:White matter (WM) injury and survival after intracerebral hemorrhage (ICH) has received insufficient attention. WM disruption surrounding the hematoma has been documented in animal models with histology, but rarely in human ICH with noninvasive means, like magnetic resonance imaging (MRI). A few human MRI studies have investigated changes in long WM tracts after ICH remote from the hematoma, like the corticospinal tract, but have not attempted to obtain an unbiased quantification of WM changes within and around the hematoma over time. This study attempts such quantification from 3 to 30 days post ictus. Thirteen patients with mild to moderate ICH underwent diffusion tensor imaging (DTI) MRI at 3, 14, and 30 days. Fractional anisotropy (FA) maps were used to calculate the volume of tissue with FA > 0.5, both within the hematoma (lesion) and in the perilesional tissue. At day 3, the percentages of both lesional and perilesional tissue with an FA > 0.5 were significantly less than contralateral, unaffected, anatomically identical tissue. This perilesional contralateral difference persisted at day 14, but there was no significant difference at day 30. The loss of perilesional tissue with FA > 0.5 increased with increasing hematoma size at day 3 and day 14. All patients had some tissue within the lesion with FA > 0.5 at all time points. This did not decrease with duration after ictus, suggesting the persistence of white matter within the hematoma/lesion. These results outline an approach to quantify WM injury, both within and surrounding the hematoma, after mild to moderate ICH using DTI MRI. This may be important for monitoring treatment strategies, such as hematoma evacuation, and assessing efficacy noninvasively.

| S-EPMC8234588 | biostudies-literature

Translational intracerebral hemorrhage: a need for transparent descriptions of fresh tissue sampling and preclinical model quality.

Project description:For years, strategies have been proposed to improve translational success in stroke research by improving the quality of animal studies. However, articles that report preclinical intracerebral hemorrhage (ICH) studies continue to lack adequate qualitative and quantitative descriptions of fresh brain tissue collection. They also tend to lack transparency about animal model quality. We conducted a systematic review of 82 ICH research articles to determine the level of detail reported for brain tissue collection. We found that only 24 (29 %) reported the volume, weight, or thickness of tissue collected and a specific description of the anatomical location. Thus, up to 71 % of preclinical ICH research articles did not properly define how fresh specimens were collected for biochemical measurements. Such omissions may impede reproducibility of results between laboratories. Although existing criteria have improved the quality of preclinical stroke studies, ICH researchers need to identify specific guidelines and strategies to avoid pitfalls, minimize bias, and increase reproducibility in this field.

| S-EPMC4560961 | biostudies-literature

Diffusion-Weighted Lesions After Intracerebral Hemorrhage: Associated MRI Findings.

Project description:The current study aimed to investigate whether diffusion-weighted imaging-positive (DWI+) lesions after acute intracerebral hemorrhage (ICH) are associated with underlying small vessel disease (SVD) or linked to the acute ICH. We included patients ≥18 years with spontaneous ICH confirmed on neuroimaging and performed 3T MRIs after a median of 11 days (interquartile range [IQR] 6-43). DWI+ lesions were assessed in relation to the hematoma (perihematomal vs. distant and ipsilateral vs. contralateral). Differences in clinical characteristics, ICH characteristics, and MRI markers of SVD between participants with or without DWI+ lesions were investigated using non-parametric tests. We observed 54 DWI+ lesions in 30 (22%) of the 138 patients (median age [IQR] 65 [55-73] years; 71% men, 59 lobar ICH) with available DWI images. We found DWI+ lesions ipsilateral (54%) and contralateral (46%) to the ICH, and 5 (9%) DWI+ lesions were located in the immediate perihematomal region. DWI+ lesion presence was associated with probable CAA diagnosis (38 vs. 15%, p = 0.01) and larger ICH volumes (37 [8-47] vs. 12 [6-24] ml, p = 0.01), but not with imaging features of SVD. Our findings suggest that DWI+ lesions after ICH are a feature of both the underlying SVD and ICH-related mechanisms.

| S-EPMC9240258 | biostudies-literature

Cortical microinfarcts on 7T MRI in patients with spontaneous intracerebral hemorrhage.

Project description:In patients with spontaneous intracerebral hemorrhage (ICH) coexisting abnormalities on brain imaging can provide clues on the etiology of the underlying small vessel disease. We examined cortical cerebral microinfarcts as a novel marker of coexistent vascular damage in ICH. Twelve patients with spontaneous ICH and 15 controls underwent 7Tesla magnetic resonance imaging (MRI). Microinfarcts were present in 9 of 12 patients with spontaneous ICH, and in 5 of 15 controls. This explorative study shows, for the first time, that microinfarcts appear to be a very common vascular comorbidity in spontaneous ICH. Future larger studies should further assess the etiological significance of these lesions.

| S-EPMC4083387 | biostudies-other

Transcriptome sequencing of human brain tissue after intracerebral hemorrhage

Project description:We used tissue bulk RNA-seq to analyze gene expression profile in the brain after intracerebral hemorrhage.

2021-09-01 | GSE167758 | GEO

Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage

Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

2024-06-11 | GSE264394 | GEO

Progress in translational research on intracerebral hemorrhage: is there an end in sight?

Project description:Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for which specific therapies and treatments remain elusive. To address this, many recent experimental and translational studies of ICH have been conducted, and these have led to several ongoing clinical trials. This review focuses on the progress of translational studies of ICH including those of the underlying causes and natural history of ICH, animal models of the condition, and effects of ICH on the immune and cardiac systems, among others. Current and potential clinical trials also are discussed for both ICH alone and with intraventricular extension.

| S-EPMC3961535 | biostudies-literature

RNA-seq of perihaematomal and anatomically matched contralateral brain tissue after intracerebral hemorrhage

Project description:Secondary injury causes death and dependence after spontaneous intracerebral haemorrhage (ICH). Having found that ICH is associated with activation of genes regulated by the transcription factor NRF2, we performed bulk RNA sequencing of perihaematomal and anatomically matched contralateral brain homogenate obtained at autopsy from a cohort of patients who died either within 24h of ICH or between 4-14 days of ICH onset, to investigate the spatiotemporal evolution of this Nrf2 activation.

2024-08-13 | E-MTAB-14323 | biostudies-arrayexpress

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