ADC mapping and T1-weighted signal changes on post-injury MRI predict seizure susceptibility after experimental traumatic brain injury

Frey, Lauren C.; Lepkin, Aaron; Schickedanz, Alyssa; Huber, Kendra M.; Brown, Mark S.; Serkova, Natalie J.

doi:10.1179/1743132813y.0000000269

Cited by 23 publications

(22 citation statements)

References 38 publications

(64 reference statements)

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“…Changes in DWI outcomes have also been reported in the FPI [23,31,37] rat model of PTE at various stages in the epileptogenic process. Of particular importance, acute and chronic hippocampal ADC changes in the FPI model were associated with electroencephalography (EEG) parameters (i.e., total number of interictal epileptiform spikes and epileptiform discharges), mossy fibre sprouting, and seizure susceptibility after a chemoconvulsant challenge [23,37].…”

Section: Diffusion-weighted Mrimentioning

confidence: 83%

“…Tractography is another DWI-based postprocessing method that allows for the assessment of structural connectivity, and holds promise in the study of epileptogenesis [38]. Notably, changes in DWI-based measures are also commonly associated with edema [37].…”

Section: Diffusion-weighted Mrimentioning

confidence: 99%

“…These agents have been used to study epileptogenesis in post-SE [16,[33][34][35][36] and FPI [32,37] rodent models, and enable the assessment of various pathologies potentially involved in the epileptogenic process, such as blood-brain barrier breakdown [16,37], mossy fiber sprouting [35], and reorganization of neural connections [31,32]. For example, studies utilizing serial Mn 2+ -enhanced imaging at 2 days and 6 weeks after SE found increased T 1 -weighted signal intensity There is persistent hypometabolism, and progressive degeneration after kainic acid-induced status epilepticus (A-C; adapted from [29]).…”

Section: Contrast Agentsmentioning

confidence: 99%

“…Common measures generated from DWI include apparent diffusion coefficient (ADC)-the magnitude of overall water diffusion in a given direction; mean diffusivity-the mean diffusivity across a number of directions; and fractional anisotropy (FA)-a value between 0 (isotropic) and 1 (anisotropic) that describes the anisotropy of diffusion [36]. In unhealthy white matter, damaged axonal membranes become less constricting to molecules and are thus less anisotropic [36,37]. Tractography is another DWI-based postprocessing method that allows for the assessment of structural connectivity, and holds promise in the study of epileptogenesis [38].…”

Section: Diffusion-weighted Mrimentioning

confidence: 99%

“…Diffusion-weighted MRI (DWI) and related methods, such as diffusion tensor and tractography analyses, are based on the quantification using magnetic resonance of the diffusivity of water molecules in the brain, which is more directionally limited (anisotropic) in white matter tracts relative to gray matter [36][37][38]. Common measures generated from DWI include apparent diffusion coefficient (ADC)-the magnitude of overall water diffusion in a given direction; mean diffusivity-the mean diffusivity across a number of directions; and fractional anisotropy (FA)-a value between 0 (isotropic) and 1 (anisotropic) that describes the anisotropy of diffusion [36].…”

Section: Diffusion-weighted Mrimentioning

confidence: 99%

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Neuroimaging the Epileptogenic Process

et al. 2014

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Epilepsy is one of the most common chronic neurological conditions worldwide. Anti-epileptic drugs (AEDs) can suppress seizures, but do not affect the underlying epileptic state, and many epilepsy patients are unable to attain seizure control with AEDs. To cure or prevent epilepsy, disease-modifying interventions that inhibit or reverse the disease process of epileptogenesis must be developed. A major limitation in the development and implementation of such an intervention is the current poor understanding, and the lack of reliable biomarkers, of the epileptogenic process. Neuroimaging represents a non-invasive medical and research tool with the ability to identify early pathophysiological changes involved in epileptogenesis, monitor disease progression, and assess the effectiveness of possible therapies. Here we will provide an overview of studies conducted in animal models and in patients with epilepsy that have utilized various neuroimaging modalities to investigate epileptogenesis.

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Section: Diffusion-weighted Mrimentioning

confidence: 83%

Section: Diffusion-weighted Mrimentioning

confidence: 99%

Section: Contrast Agentsmentioning

confidence: 99%

Section: Diffusion-weighted Mrimentioning

confidence: 99%

Section: Diffusion-weighted Mrimentioning

confidence: 99%

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Neuroimaging the Epileptogenic Process

et al. 2014

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Diffusion MRI and the detection of alterations following traumatic brain injury

Hutchinson

Schwerin

Avram

et al. 2017

J of Neuroscience Research

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This article provides a review of brain tissue alterations that may be detectable using diffusion MRI (dMRI) approaches and an overview and perspective on the modern dMRI toolkits for characterizing alterations that follow traumatic brain injury (TBI). Non-invasive imaging is a cornerstone of clinical treatment of TBI and has become increasingly used for pre-clinical and basic research studies. In particular, quantitative MRI methods have the potential to distinguish and evaluate the complex collection of neurobiological responses to TBI arising from pathology, neuroprotection and recovery. Diffusion MRI provides unique information about the physical environment in tissue and can be used to probe physiological, architectural and microstructural features. While well-established approaches such as diffusion tensor imaging (DTI) are known to be highly sensitive to changes in the tissue environment, more advanced diffusion MRI techniques have been developed that may offer increased specificity or new information for describing abnormalities. These tools are promising, but incompletely understood in the context of TBI. Furthermore, model dependencies and relative limitations may impact the implementation of these approaches and the interpretation of abnormalities in their metrics. The objective of this paper is to present a basic review and comparison across diffusion MRI methods as they pertain to the detection of the most commonly observed tissue and cellular alterations following TBI.

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Silibinin inhibits hypoxia‐induced HIF‐1α‐mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics

Deep

Kumar

Nambiar

et al. 2016

Molecular Carcinogenesis

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Hypoxia is associated with aggressive phenotype and poor prognosis in prostate cancer (PCa) patients suggesting that PCa growth and progression could be controlled via targeting hypoxia-induced signaling and biological effects. Here, we analyzed silibinin (a natural flavonoid) efficacy to target cell growth, angiogenesis and metabolic changes in human PCa, LNCaP and 22Rv1 cells under hypoxic condition. Silibinin treatment inhibited the proliferation, clonogenicity and endothelial cells tube formation by hypoxic (1% O2) PCa cells. Interestingly, hypoxia promoted a lipogenic phenotype in PCa cells via activating acetyl-Co A carboxylase (ACC) and fatty acid synthase (FASN) that was inhibited by silibinin treatment. Importantly, silibinin treatment strongly decreased hypoxia-induced HIF-1α expression in PCa cells together with a strong reduction in hypoxia-induced NADPH oxidase (NOX) activity. HIF-1α overexpression in LNCaP cells significantly increased the lipid accumulation and NOX activity; however, silibinin treatment reduced HIF-1α expression, lipid levels, clonogenicity and NOX activity even in HIF-1α overexpressing LNCaP cells. In vivo, silibinin feeding (200 mg/kg body weight) to male nude mice with 22Rv1 tumors, specifically inhibited tumor vascularity (measured by dynamic contrast-enhanced MRI) resulting in tumor growth inhibition without directly inducing necrosis (as revealed by diffusion-weighted MRI). Silibinin feeding did not significantly affect tumor glucose uptake measured by FDG-PET; however, reduced the lipid synthesis measured by quantitative 1H-NMR metabolomics. IHC analyses of tumor tissues confirmed that silibinin feeding decreased proliferation and angiogenesis as well as reduced HIF-1α, FASN and ACC levels. Together, these findings further support silibinin usefulness against PCa through inhibiting hypoxia-induced signaling.

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ADC mapping and T1-weighted signal changes on post-injury MRI predict seizure susceptibility after experimental traumatic brain injury

Cited by 23 publications

References 38 publications

Neuroimaging the Epileptogenic Process

Neuroimaging the Epileptogenic Process

Diffusion MRI and the detection of alterations following traumatic brain injury

Silibinin inhibits hypoxia‐induced HIF‐1α‐mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics

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