In vivo metabolic imaging of Traumatic Brain Injury.

Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway. We then used the colony-stimulating factor-1 receptor inhibitor PLX5622 to deplete brain resident microglia prior to and after CCI, in order to confirm that modulations of HP [1-13C] lactate-to-pyruvate ratios were linked to microglial activation. Despite CCI, the HP [1-13C] lactate-to-pyruvate ratio at the injury cortex of microglia-depleted animals at 7 days post-injury remained unchanged compared to contralateral hemisphere, and PDH activity was not affected. Altogether, our results demonstrate that HP [1-13C] pyruvate has great potential for in vivo non-invasive detection of cerebral metabolism post-TBI, providing a new tool to monitor the effect of therapies targeting microglia/macrophages activation after TBI

A importância dos novos sistemas para a logística do comércio exterior

The present work aims to demonstrate how the new foreign trade systems help in the logistics of the same. Among them, the Single Foreign Trade Portal, which reformulates the importation and exportation operations. In this context, the Single Export Declaration (DU-E) is inserted, which promises the elimination of documents and reduction of government requirements, and the Single Import Declaration (DUIMP) that can be registered even before the goods arrives in the country, reducing time and bureaucracy. With this, the country's GDP tends to grow, making Brazil more competitive.O presente trabalho tem como objetivo demonstrar como os novos sistemas do comércio exterior ajudam na logística do mesmo. Dentre eles cabe ressaltar o Portal Único de Comércio Exterior, que reformula as operações de importação e exportação. Neste contexto está inserida a Declaração Única de Exportação (DU-E), que promete a eliminação dos documentos e redução nas exigências do governo, e a Declaração Única de Importação (DUIMP) que poderá ser registrada antes mesmo da mercadoria chegar ao país, garantindo redução de tempo e burocracia, gerando, com isso, um possível crescimento no PIB o que torna o Brasil, consequentemente, mais competitivo

Imaging Brain Metabolism Using Hyperpolarized 13C Magnetic Resonance Spectroscopy

Aberrant metabolism is a key factor in many neurological disorders. The ability to measure such metabolic impairment could lead to improved detection of disease progression, and development and monitoring of new therapeutic approaches. Hyperpolarized 13C magnetic resonance spectroscopy (MRS) is a developing imaging technique that enables non-invasive measurement of enzymatic activity in real time in living organisms. Primarily applied in the fields of cancer and cardiac disease so far, this metabolic imaging method has recently been used to investigate neurological disorders. In this review, we summarize the preclinical research developments in this emerging field, and discuss future prospects for this exciting technology, which has the potential to change the clinical paradigm for patients with neurological disorders

Imaging immunomodulatory treatment responses in a multiple sclerosis mouse model using hyperpolarized 13C metabolic MRI.

BackgroundIn recent years, the ability of conventional magnetic resonance imaging (MRI), including T1 contrast-enhanced (CE) MRI, to monitor high-efficacy therapies and predict long-term disability in multiple sclerosis (MS) has been challenged. Therefore, non-invasive methods to improve MS lesions detection and monitor therapy response are needed.MethodsWe studied the combined cuprizone and experimental autoimmune encephalomyelitis (CPZ-EAE) mouse model of MS, which presents inflammatory-mediated demyelinated lesions in the central nervous system as commonly seen in MS patients. Using hyperpolarized 13C MR spectroscopy (MRS) metabolic imaging, we measured cerebral metabolic fluxes in control, CPZ-EAE and CPZ-EAE mice treated with two clinically-relevant therapies, namely fingolimod and dimethyl fumarate. We also acquired conventional T1 CE MRI to detect active lesions, and performed ex vivo measurements of enzyme activities and immunofluorescence analyses of brain tissue. Last, we evaluated associations between imaging and ex vivo parameters.ResultsWe show that hyperpolarized [1-13C]pyruvate conversion to lactate is increased in the brain of untreated CPZ-EAE mice when compared to the control, reflecting immune cell activation. We further demonstrate that this metabolic conversion is significantly decreased in response to the two treatments. This reduction can be explained by increased pyruvate dehydrogenase activity and a decrease in immune cells. Importantly, we show that hyperpolarized 13C MRS detects dimethyl fumarate therapy, whereas conventional T1 CE MRI cannot.ConclusionsIn conclusion, hyperpolarized MRS metabolic imaging of [1-13C]pyruvate detects immunological responses to disease-modifying therapies in MS. This technique is complementary to conventional MRI and provides unique information on neuroinflammation and its modulation