Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Nov 2017
ReviewImplications of neurovascular uncoupling in functional magnetic resonance imaging (fMRI) of brain tumors.
Functional magnetic resonance imaging (fMRI) serves as a critical tool for presurgical mapping of eloquent cortex and changes in neurological function in patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling remains intact during brain tumor progression, and that measured changes in cerebral blood flow (CBF) are correlated with neuronal function. Recent preclinical and clinical studies have demonstrated that even low-grade brain tumors can exhibit neurovascular uncoupling (NVU), which can confound interpretation of fMRI data. ⋯ Next, we synthesize results from preclinical and clinical studies to illustrate how brain tumor induced NVU affects fMRI data interpretation. We examine advances in functional imaging methods that permit the clinical evaluation of brain tumors with NVU. Finally, we discuss how the suppression of anomalous tumor blood vessel formation with antiangiogenic therapies can "normalize" the brain tumor vasculature, and potentially restore neurovascular coupling.
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J. Cereb. Blood Flow Metab. · Sep 2017
MRI-based mismatch detection in acute ischemic stroke: Optimal PWI maps and thresholds validated with PET.
Perfusion-weighted (PW) magnetic resonance imaging (MRI) is used to detect penumbral tissue in acute stroke, but the selection of optimal PW-maps and thresholds for tissue at risk detection remains a matter of debate. We validated the performance of PW-maps with 15O-water-positron emission tomography (PET) in a large comparative PET-MR cohort of acute stroke patients. In acute and subacute stroke patients with back-to-back MRI and PET imaging, PW-maps were validated with 15O-water-PET. ⋯ A receiver operating characteristic (ROC) curve analysis was performed to specify the accuracy and the optimal critical flow threshold of each PW-map as defined by PET. In 53 patients, (stroke to imaging: 9.8 h; PET to MRI: 52 min) PW-time-to-maximum (Tmax) with a threshold >6.1 s (AUC = 0.94) and non-deconvolved PW-time-to-peak (TTP) >4.8 s (AUC = 0.93) showed the best performance to detect the CF threshold as defined by PET. PW-Tmax with a threshold >6.1 s and TTP with a threshold >4.8 s are the most predictive in detecting the CF threshold for MR-based mismatch definition.
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J. Cereb. Blood Flow Metab. · Sep 2017
Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.
Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. ⋯ A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.
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J. Cereb. Blood Flow Metab. · Aug 2017
Noninvasive optical monitoring of critical closing pressure and arteriole compliance in human subjects.
The critical closing pressure ( CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure ( ABP) at which cerebral blood flow approaches zero, and their difference ( ABP - CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. ⋯ Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.
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J. Cereb. Blood Flow Metab. · Aug 2017
Posttraumatic therapeutic hypothermia alters microglial and macrophage polarization toward a beneficial phenotype.
Posttraumatic inflammatory processes contribute to pathological and reparative processes observed after traumatic brain injury (TBI). Recent findings have emphasized that these divergent effects result from subsets of proinflammatory (M1) or anti-inflammatory (M2) microglia and macrophages. Therapeutic hypothermia has been tested in preclinical and clinical models of TBI to limit secondary injury mechanisms including proinflammatory processes. ⋯ RT-PCR of M1-associated genes including iNOS and IL-1β was significantly reduced with hypothermia while M2-associated genes including arginase and CD163 were significantly increased compared to normothermic conditions. The injury-induced increased expression of the chemokine Ccl2 was also reduced with PTH. These studies provide a link between temperature-sensitive alterations in macrophage/microglia activation and polarization toward a M2 phenotype that could be permissive for cell survival and repair.