Dataset Information

Brain imaging in stroke: insight beyond diagnosis.

ABSTRACT: Stroke, whether hemorrhagic or ischemic in nature, has the ability to lead to devastating and debilitating patient outcomes, which not only has direct implications from a healthcare standpoint, but its effects are longstanding and they impact the community as a whole. For decades, the goal of advancement and refinement in imaging modalities has been to develop the most precise, convenient, widely available and reproducible interpretable modality for the detection of stroke, not only in its hyperacute phase, but a method to be able to predict its evolution through the natural course of disease. Diagnosis is one of the most important initial roles, which imaging fulfills after the identification of existent pathology. However, imaging fulfills an even more important goal by using a combination of imaging modalities and their precise interpretation, which lends itself to understanding the mechanisms and pathophysiology of underlying disease, and therefore guides therapeutic decision-making in a patient-tailored fashion. This review explores the most commonly used brain imaging modalities, computer tomography, and magnetic resonance imaging, with an aim to demonstrate their dynamic use in uncovering stroke mechanism, facilitating prognostication, and potentially guiding therapy.

SUBMITTER: Nour M

PROVIDER: S-EPMC3144982 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Brain imaging in stroke: insight beyond diagnosis.

Nour May M Liebeskind David S DS

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20110701 3

Stroke, whether hemorrhagic or ischemic in nature, has the ability to lead to devastating and debilitating patient outcomes, which not only has direct implications from a healthcare standpoint, but its effects are longstanding and they impact the community as a whole. For decades, the goal of advancement and refinement in imaging modalities has been to develop the most precise, convenient, widely available and reproducible interpretable modality for the detection of stroke, not only in its hyper ...[more]

PMID: 21556679

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Project description:Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines and reduce the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most attractive reaction for this purpose is currently the tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetrazines (Tzs). Pretargeted imaging beyond the blood-brain barrier (BBB) is challenging and has not been reported thus far. In this study, we developed Tz imaging agents that are capable of ligating in vivo to targets beyond the BBB. We chose to develop 18F-labeled Tzs as they can be applied to positron emission tomography (PET) - the most powerful molecular imaging technology. Fluorine-18 is an ideal radionuclide for PET due to its almost ideal decay properties. As a non-metal radionuclide, fluorine-18 also allows for development of Tzs with physicochemical properties enabling passive brain diffusion. To develop these imaging agents, we applied a rational drug design approach. This approach was based on estimated and experimentally determined parameters such as the BBB score, pretargeted autoradiography contrast, in vivo brain influx and washout as well as on peripheral metabolism profiles. From 18 initially developed structures, five Tzs were selected to be tested for their in vivo click performance. Whereas all selected structures clicked in vivo to TCO-polymer deposited into the brain, [18F]18 displayed the most favorable characteristics with respect to brain pretargeting. [18F]18 is our lead compound for future pretargeted neuroimaging studies based on BBB-penetrant monoclonal antibodies. Pretargeting beyond the BBB will allow us to image targets in the brain that are currently not imageable, such as soluble oligomers of neurodegeneration biomarker proteins. Imaging of such currently non-imageable targets will allow early diagnosis and personalized treatment monitoring. This in turn will accelerate drug development and greatly benefit patient care.

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Project description:Maintaining blood-brain barrier (BBB) integrity is crucial for the homeostasis of the central nervous system. Structurally comprising the BBB, brain endothelial cells interact with pericytes, astrocytes, neurons, microglia, and perivascular macrophages in the neurovascular unit. Brain ischemia unleashes a profound neuroinflammatory response to remove the damaged tissue and prepare the brain for repair. However, the intense neuroinflammation occurring during the acute phase of stroke is associated with BBB breakdown, neuronal injury, and worse neurological outcomes. Here, we critically discuss the role of neuroinflammation in ischemic stroke pathology, focusing on the BBB and the interactions between central nervous system and peripheral immune responses. We highlight inflammation-driven injury mechanisms in stroke, including oxidative stress, increased MMP (matrix metalloproteinase) production, microglial activation, and infiltration of peripheral immune cells into the ischemic tissue. We provide an updated overview of imaging techniques for in vivo detection of BBB permeability, leukocyte infiltration, microglial activation, and upregulation of cell adhesion molecules following ischemic brain injury. We discuss the possibility of clinical implementation of imaging modalities to assess stroke-associated neuroinflammation with the potential to provide image-guided diagnosis and treatment. We summarize the results from several clinical studies evaluating the efficacy of anti-inflammatory interventions in stroke. Although convincing preclinical evidence suggests that neuroinflammation is a promising target for ischemic stroke, thus far, translating these results into the clinical setting has proved difficult. Due to the dual role of inflammation in the progression of ischemic damage, more research is needed to mechanistically understand when the neuroinflammatory response begins the transition from injury to repair. This could have important implications for ischemic stroke treatment by informing time- and context-specific therapeutic interventions.

Project description:Background: The clinical outcome of patients suffering from stroke is dependent on multiple factors. The features of the lesion itself play an important role but clinical recovery is remarkably influenced by the plasticity mechanisms triggered by the stroke and occurring at a distance from the lesion. The latter translate into functional and structural changes of which cortical thickness might be easy to quantify one of the main players. However, studies on the changes of cortical thickness in brain areas beyond stroke lesion and their relationship to sensory-motor recovery are sparse. Objectives: To evaluate the effects of cerebral stroke on cortical thickness (CT) beyond the stroke lesion and its association with sensory-motor recovery. Materials and Methods: Five electronic databases (PubMed, Embase, Web of Science, Scopus and the Cochrane Library) were searched. Methodological quality of the included studies was assessed with the Newcastle-Ottawa Scale for non-randomized controlled trials and the Risk of Bias Cochrane tool for randomized controlled trials. Results: The search strategy retrieved 821 records, 12 studies were included and risk of bias assessed. In most of the included studies, cortical thinning was seen at the ipsilesional motor area (M1). Cortical thinning can occur beyond the stroke lesion, typically in regions anatomically connected because of anterograde degeneration. Nonetheless, studies also reported cortical thickening of regions of the unaffected hemisphere, likely related to compensatory plasticity. Some studies revealed a significant correlation between changes in cortical thickness of M1 or somatosensory (S1) cortical areas and motor function recovery. Discussion and Conclusions: Following a stroke, changes in cortical thickness occur both in regions directly connected to the stroke lesion and in contralateral hemisphere areas as well as in the cerebellum. The underlying mechanisms leading to these changes in cortical thickness are still to be fully understood and further research in the field is needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020200539; PROSPERO 2020, identifier: CRD42020200539.

Dataset Information

Brain imaging in stroke: insight beyond diagnosis.

Publications

Brain imaging in stroke: insight beyond diagnosis.

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