Changes In Brain Perfusion Research Articles

Semantic verbal fluency brain network: delineating a physiological basis for the functional hubs using dual-echo ASL and graph theory approach

Objective. Semantic verbal fluency (SFV) is a cognitive process that engages and modulates specific brain areas related to language comprehension and production, decision making, response inhibition, and memory retrieval. The impairment of the brain network responsible for these functions is related to various neurological conditions, and different strategies have been proposed to assess SVF-related deficits in such diseases. In the present study, the concomitant changes of brain perfusion and functional connectivity were investigated during the resting state and SVF task performance. Approach. Arterial spin labeling (ASL), a perfusion-based magnetic resonance imaging (MRI) method, was used with a pseudocontinuous labeling approach and dual-echo readout in 28 healthy right-handed Brazilian Portuguese speakers. The acquisition was performed in a resting state condition and during the performance of a SVF task. Main results. During task performance, a significant increase in cerebral blood flow (CBF) was observed in language-related regions of the frontal lobe, including Brodmann’s areas 6, 9, 45, and 47, associated with semantic processing, word retrieval, and speech motor programming. Such regions, along with the posterior cingulate, showed a crucial role in the SVF functional network, assessed by seed-to-voxel and graph analysis. Our approach successfully overcame the generalization problem regarding functional MRI (fMRI) graph analysis with cognitive, task-based paradigms. Moreover, the CBF maps enabled the functional assessment of orbital frontal and temporal regions commonly affected by magnetic susceptibility artifacts in conventional T2*-weighted fMRI approaches. Significance. Our results demonstrated the capability of ASL to evaluate perfusion alterations and functional patterns simultaneously regarding the SVF network providing a quantitative physiological basis to functional hubs in this network, which may support future clinical studies.

Unlocking in COVID Times: The Neurosurgical Way

AbstractThe humankind is facing one of the worst nightmares in the form of the ongoing Corona crisis. The pandemic has spread all across the globe and we are struggling to deal with its might. All nations have made their own strategies to deal with this situation and mainly a phase of lockdown has been the savior in most countries, especially India, where it was enforced early and well in time. After a successful lockdown, there is a phase of unlocking, which is equally important. One should exercise caution in that this should be done gradually and phased, with all the precautions in place and without any complacency. Neurosurgeons are faced with a situation pertaining to those afflicted by posterior fossa lesions with hydrocephalus. They are treated with ventriculoperitoneal shunt, but sometimes they develop reverse tentorial herniation. This needs prompt evaluation and intervention and carries a poor prognosis if untreated. Another situation is where bifrontal contusions need decompressive surgery; some patients develop encephaloceles and extradural hematomas following successful surgery and complicate the prognosis. Both situations emerge due to sudden decompression, leading to quick changes in brain pressure and perfusion. The solution is slow and careful decompression, with all precautions in place despite the temptation of eureka moments. A similar response could be desirous over the course of our unlocking period. Hope this wisdom brings us good results in these Corona times.

Age, BMI and diabetes as independent predictors of brain hypoperfusion.

Cerebral blood flow abnormalities are supposed to be potential risk factors for developing cognitive dysfunction in the general population. Aging, obesity and type 2 diabetes mellitus are associated with perfusion abnormalities leading to cognitive impairment, neurodegeneration and future development of dementia. In our study, we aimed at identifying independent factors that contribute to the appearance of regional brain perfusion changes besides those that are already known. Forty-three type 2 diabetic and twenty-six obese patients were enrolled. After the intravenous administration of 740 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO), all subjects underwent brain perfusion SPECT imaging applying AnyScan S Flex dual-head gamma camera (Mediso, Hungary). Using Philips Achieva 3T scanner brain resting-state functional MRI was also performed. The SPECT and MRI images were co-registered and transformed to the MNI152 atlas space so that data of the following standard volumes of interest (VOIs) could be obtained: frontal lobe, parietal lobe, temporal lobe, occipital lobe, limbic region, cingulate, insula, basal ganglia, cerebrum, limbic system and brain stem. Using the SPSS 25 statistical software package, general linear regression analysis, Student's t-test, and Mann-Whitney U-test were applied for statistical analyses. Multivariate linear analysis identified that BMI and age are significantly (p < 0.0001) associated with perfusion, and patient group was slightly above threshold (p = 0.0524). We also found that the presence of diabetes was an independent significant predictor of normalized regional brain perfusion only in the insula (p < 0.001). Other independent predictors of normalized regional brain perfusion were: age in the insula (p < 0.001) and in the limbic region (p < 0.01), and BMI in the brain stem (p < 0.01). Age and BMI proved to be general, and diabetes regional predictor of brain hypoperfusion. BMI appeared to be a novel factor affecting brain perfusion. In one specific region, the insula, we detected a difference between the obese and the diabetic group. These findings may be significant in the understanding of the development of cognitive impairment in metabolic diseases.

Dual-phase 18F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer’s disease

BackgroundThis study investigated changes in brain perfusion and Aβ burden according to the progression of Alzheimer’s disease (AD) by using a dual-phase 18F-florbetaben (FBB) PET protocol. MethodsSixty subjects, including 12 with Aβ-negative normal cognition (Aβ−NC), 32 with Aβ-positive mild cognitive impairment (Aβ+MCI), and 16 with Aβ-positive AD (Aβ+AD), were enrolled. A dynamic PET scan was obtained in the early phase (0–10 min, eFBB) and delayed phase (90–110 min, dFBB), which were then averaged into a single frame, respectively. In addition to the averaged eFBB, an R1 parametric map was calculated from the eFBB scan based on a simplified reference tissue model (SRTM). Between-group regional and voxel-wise analyses of the images were performed. The associations between cognitive profiles and PET-derived parameters were investigated. ResultsBoth the R1 and eFBB perfusion reductions in the cortical regions were not significantly different between the Aβ−NC and Aβ+MCI groups, while they were significantly reduced from the Aβ+MCI to Aβ+AD groups in regional and voxel-wise analyses. However, cortical Aβ depositions on dFBB were not significantly different between the Aβ+MCI and Aβ+AD groups. There were strong positive correlations between the R1 and eFBB images in regional and voxel-wise analyses. Both perfusion components showed significant correlations with general and specific cognitive profiles. ConclusionThe results of this study demonstrated the feasibility of dual-phase 18F-FBB PET to evaluate different trajectories of dual biomarkers for neurodegeneration and Aβ burden over the course of AD. In addition, both eFBB and SRTM-based R1 can provide robust indices of brain perfusion.

Migraine attacks as a result of hypothalamic loss of control

Migraine is a complex neurological disorder affecting approximately 12% of the population. The pathophysiology is not yet fully understood, however the clinical features of the disease, such as the cyclic behaviour of attacks and vegetative symptoms, suggest a prominent role of the hypothalamus. Previous research has observed neuronal alterations at different time points during the migraine interval, specifically just before the headache is initiated. We therefore aimed to assess the trajectory of migraineurs’ brain activity over an entire migraine cycle.Using functional magnetic resonance imaging (fMRI) with pseudo-continuous arterial spin labelling (ASL), we designed a longitudinal intra-individual study to detect the rhythmicity of (1) the cerebral perfusion and (2) the hypothalamic connectivity over an entire migraine cycle. Twelve episodic migraine patients were examined in 82 sessions during spontaneous headache attacks with follow-up recordings towards the next attack.We detected cyclic changes of brain perfusion in the limbic circuit (insula and nucleus accumbens), with the highest perfusion during the headache attack. In addition, we found an increase of hypothalamic connectivity to the limbic system over the interictal interval towards the attack, then collapsing during the headache phase.The present data provide strong evidence for the predominant role of the hypothalamus in generating migraine attacks. Due to a genetically-determined cortical hyperexcitability, migraineurs are most likely characterised by an increased susceptibility of limbic neurons to the known migraine trigger. The hypothalamus as a metronome of internal processes is suggested to control these limbic circuits: migraine attacks may occur as a result of the hypothalamus losing control over the limbic system. Repetitive psychosocial stress, one of the leading trigger factors reported by patients, might make the limbic system even more vulnerable and lead to a premature triggering of a migraine attack. Potential therapeutic interventions are therefore suggested to strengthen limbic circuits with dedicated medication or psychological approaches.

Brain Contrast-Enhanced Ultrasound Evaluation of a Pediatric Swine Model.

Brain injury remains a leading cause of morbidity and mortality in children. We evaluated the feasibility of using a pediatric swine model to develop contrast-enhanced ultrasound (CEUS)-based measures of brain perfusion for clinical application in various types of brain injury monitoring. Six-week-old, 10-kg swine (N = 10) were anesthetized, and an acoustic window was created in the right frontal cranium to provide visualization of an oblique coronal plane and bilateral thalami. Ultrasound contrast agent was administered via a femoral venous catheter as a weight-based (0.03 mL/kg) bolus. After localization of the imaging plane, CEUS cine clips were acquired for 90 seconds. Bolus injection of contrast agent provided global visualization of cerebral perfusion and highlighted microvasculature in the brain. Preliminary evaluation of bolus kinetics in piglets showed a central gray nuclei-to-cortex ratio similar to human infants with a steep wash-in that crossed and remained above the 1.0 threshold for most of the enhancement period. We demonstrated the similarity in brain perfusion between piglets and human infants, specifically central gray nuclei-to-cortex ratio, showing preliminary feasibility of its use as a pediatric model of brain perfusion. Contrast-enhanced ultrasound can be performed at the bedside as a minimally invasive procedure, and quantitative CEUS may provide critical information regarding changes in brain perfusion as a result of injury or as a response to therapy.

Pharmaco-fUS: Quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice

There is a critical need for reliable quantitative biomarkers to assess functional brain alterations in mouse models of neuropsychiatric diseases, but current imaging methods measuring drug effects through the neurovascular coupling, face issues including poor sensitivity, drug-induced changes in global brain perfusion and the effects of anesthesia.Here we demonstrate the proof-of-concept of a minimally-invasive fUS imaging approach to detect the acute cholinergic modulatory effects of Scopolamine (ScoP) on functional brain connectivity in awake and behaving mice, through the intact skull. A machine-learning algorithm constructed an ad-hoc pharmacological score from the ScoP-induced changes in connectivity patterns of five mice. The discrimination model shows important ScoP-induced increase of the hippocampo-cortical connectivity. The pharmacological score led to robust discrimination of ScoP treatment from baseline in an independent dataset and showed, in another independent group, dose-dependent specific effects of central cholinergic modulation of functional connectivity, independent from global brain perfusion changes. In conclusion, we introduce pharmaco-fUS as a simple, robust, specific and sensitive modality to monitor drug effects on perfusion and functional connectivity in the awake mouse brain.

The Developmental Trajectory of Cancer-Related Cognitive Impairment in Breast Cancer Patients: A Systematic Review of Longitudinal Neuroimaging Studies.

This systematic review explored the neurobiological mechanisms underlying the clinical time course of cancer-related cognitive impairment (CRCI) in breast cancer patients through the review of longitudinal neuroimaging studies. Before chemotherapy, results reported no evidence for neuropsychological, structural (gray matter) and brain perfusion changes. However, functional brain alterations were evident and revealed a frontoparietal hyperactivation during working memory tasks. Fatigue and number of days since surgery were the two suggested confounding factors. Acutely after chemotherapy, this review found no evidence for neuropsychological changes while suggesting a pattern of frontal structural, perfusion and functional brain abnormalities. These findings seemed to be dependent on age, menopausal status at baseline, and fMRI task performed. Years after chemotherapy, results revealed evidence of partial neuropsychological, structural, and functional brain recovery. Regarding brain abnormality, this review suggested that it may begin quite early in the disease course, be more prominent shortly after chemotherapy and partially recover over time. Several hypotheses underlying these changes were discussed. The present review also provided important information for developing a time-specific treatment and prevention strategies and for the consideration of functional neuroimaging as a relevant tool for CRCI diagnosis, clinical monitoring, and intervention studies. The findings also suggested the need to implement studies with longitudinal designs, including a pre-treatment assessment, since cross-sectional studies were not able to detect this pattern of recovery over time, supporting only the theory of brain abnormalities, in breast cancer survivors.

Arterial spin labeling perfusion in neonates

Abnormal brain perfusion is a key mechanism underlying neonatal brain injury. Understanding the mechanisms leading to brain perfusion changes in high-risk neonates and how these alterations may influence brain development is key to improve therapeutic strategies preventing brain injury and the neurodevelopmental outcome of these infants. To date, several studies demonstrated that Arterial Spin Labeling is a reliable tool to accurately and non-invasively analyze brain perfusion, facilitating the understanding of normal and pathological mechanisms underlying neonatal brain maturation and injury. This paper provides an overview of the normal pattern of brain perfusion on Arterial Spin Labeling in term and preterm neonates, and reviews perfusion abnormalities associated with common neonatal neurological disorders.

Diagnostic utility of arterial spin labeling in identifying changes in brain perfusion in patients with carbon monoxide poisoning

ObjectiveCarbon monoxide (CO) poisoning is one of the most common poisonings worldwide. The affinity of hemoglobin for CO is significantly higher than that for oxygen, and the formation of carboxy-hemoglobin leads to a decrease in the capacity of blood to transport oxygen to tissues, tissue hypoxia, and early perfusion changes in the affected tissue. This study aimed to investigate the utility of arterial spin labeling perfusion imaging (ASL-PI) in revealing cerebral vascular hemodynamic changes in patients presenting to the emergency room with CO poisoning and to compare findings with those from diffusion-weighted imaging (DWI). MethodThis study was conducted between November 2016 and May 2019 and was approved by the local ethics committee. DWI and ASL-PI examinations were performed in 83 patients who presented to the emergency room with CO poisoning. Four regions—the cerebral cortex, basal ganglia, cerebral white matter, and cerebellum—were evaluated for alterations in perfusion and diffusion, and findings from DWI and ASL-PI were compared. ResultsThe study group included 39 (50.6%) females and 38 (49.4%) males, with a mean (±SD) age of 40.08 ± 20.41 years (range, 7–86 years). DWI revealed restricted diffusion in 10 regions in 6 (7.8%) patients, including the basal ganglia (n = 2), cerebral white matter (n = 2), cerebral cortex (n = 3), and the cerebellum (n = 3). ASL-PI revealed hypo-perfusion in 64 regions in 36 (46.8%) patients, including the basal ganglia (n = 21), cerebral white matter (n = 12), cerebral cortex (n = 23), and cerebellum (n = 7). ConclusionASL-PI provided additional information when used to identify perfusion changes in the brains of individuals who experienced CO poisoning and was superior to DWI as it revealed early changes in the brain. Considering its limitations, ASL-PI can be routinely used with DWI in cases of CO poisoning.

Non-invasive characterization of amyotrophic lateral sclerosis in a hTDP-43A315T mouse model: A PET-MR study

Currently TAR DNA binding protein 43 (TDP-43) pathology, underlying Amyotrophic Lateral Sclerosis (ALS), remains poorly understood which hinders both clinical diagnosis and drug discovery efforts. To better comprehend the disease pathophysiology, positron emission tomography (PET) and multi-parametric magnetic resonance imaging (mp-MRI) provide a non-invasive mode to investigate molecular, structural, and neurochemical abnormalities in vivo. For the first time, we report the findings of a longitudinal PET-MR study in the TDP-43A315T ALS mouse model, investigating disease-related changes in the mouse brain. 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET showed significantly lowered glucose metabolism in the motor and somatosensory cortices of TDP-43A315T mice whereas metabolism was elevated in the region covering the bilateral substantia nigra, reticular and amygdaloid nucleus between 3 and 7 months of age, as compared to non-transgenic controls. MR spectroscopy data showed significant changes in glutamate + glutamine (Glx) and choline levels in the motor cortex and hindbrain of TDP-43A315T mice compared to controls. Cerebral blood flow (CBF) measurements, using an arterial spin labelling approach, showed no significant age- or group-dependent changes in brain perfusion. Diffusion MRI indices demonstrated transient changes in different motor areas of the brain in TDP-43A315T mice around 14 months of age. Cytoplasmic TDP-43 proteinaceous inclusions were observed in the brains of symptomatic, 18-month-old mice, but not in non-symptomatic transgenic or wild-type mice. Our results reveal that disease- and age-related functional and neurochemical alterations, together with limited structural changes, occur in specific brain regions of transgenic TDP-43A315T mice, as compared to their healthy counterparts. Altogether these findings shed new light on TDP-43A315T disease pathogenesis and may prove useful for clinical management of ALS.

Cortical hypoperfusion in patients with idiopathic rapid eye movement sleep behavior disorder detected with arterial spin-labeled perfusion MRI.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is an important risk factor for α-synucleinopathy. We investigated alterations in the cerebral blood flow (CBF) based on arterial spin-labeled (ASL) imaging in patients with iRBD to determine brain perfusion changes associated with the disorder. Fifteen patients with iRBD and twenty age-gender-matched healthy controls were enrolled. Cortical perfusions were compared between the two groups after the ASL data was co-registered to the high-resolution T1-weighted images. No significant differences were detected between the groups in regard to age, gender, education, or UPDRS-III score. The iRBD group showed a lower MMSE score than the healthy controls (27.07 ± 2.25 vs. 28.55 ± 1.23, p < 0.05). Compared with the healthy controls, the iRBD group showed significantly decreased CBF values in the right inferior frontal gyrus, right middle frontal gyrus, and right insula (p < 0.05 corrected). The cortical hypoperfusion areas in patients with iRBD were similar to the patterns in patients with α -synucleinopathies. ASL perfusion MRI is a potential approach to find biomarkers in preclinical stages of α -synucleinopathies.

Efficacy of NMDA receptor antagonist on regional cerebral blood flow in Parkinson's disease with dementia

Although the treatment efficacy of memantine in Parkinson’s disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using 99mTc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD. The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p = 0.32), sum of box of CDR (p = 0.49), MMSE (p = 0.61), GDS (p = 0.79), and NPI (p = 0.23) were not significant in the PDD patients. Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

Improved functional brain anomalies after personalized rTMS relative to classical rTMS and tDCS in resistant depression

Introduction The iADAPT study - Imagery guided Anti-Depressive Adaptive Personalized TMS ( NCT02863380 ) - is a double-blind randomized cross-over study designed to assess the feasibility and efficiency of personalizing rTMS protocol, based on the functional imaging of single subjects, relative to classical rTMS and tDCS. Method Brain imaging included two kinds of ASL sequences, converted in rCBF, repeated in three different sessions, using different functional paradigms and contrasted to 38 normal controls. The tDCS protocol used an F3 anodal positioning (20 min, 2 mA). Classical rTMS used F3 positioning (3000 pulses, 120%, 10 Hz). Last personalized rTMS was designed to correct the rCBF anomalies. Thirty bilateral targets were planned to cover the reachable parts of the complex regions with abnormal perfusion. Coil positioning used a robotic neuronavigated device. In case of hypo-perfusion, targets were stimulated using the same protocol than HF-rTMS. There were 2 sessions per day for 10 days in each of the 3 conditions (personalized rTMS, classical rTMS, tDCS) Changes in brain perfusion were assessed on rCBF-ASL imaging and changes in connectivity were assessed on the BOLD signal. Results We report on the first 14 completers. Four patients had significant MRI anomalies (29%). The left prefrontal region was hypo-perfused in 8 subjects (57%), and hyper-perfused in 2 (15%). The right prefrontal region was hypo-perfused in 10 subjects (71%). Six patients remitted (43%) and further 2 of them responded (14%). Quite all remissions (5/6) occurred during or within a week post personalized rTMS. Brain imaging mimicked clinical improvement with perfusion increases in a large fronto-parietal network in the personalized condition (P Conclusion These are preliminary evidences that personalizing rTMS might improve its biological effect and clinical outcome.

Effect of cervical manipulation on vertebral artery and cerebral haemodynamics in patients with chronic neck pain: a crossover randomised controlled trial

ObjectiveIt is hypothesised that cervical manipulation may increase the risk of cerebrovascular accidents. We aimed to determine whether cervical spine manipulation is associated with changes in vertebral artery and cerebrovascular...

Neurobiological Differences Between Aggression and Agitation in Persons with DementiaAffiliation

Background Controversy exists about definition of agitation and especially about inclusion of aggression as a part of agitation in people with dementia. Methods: Papers describing neurobiological indices related to behavioral symptoms of dementia were reviewed. Papers comparing indices in persons exhibiting aggression and persons exhibiting agitation were selected for this review. Results The survey found seven papers which compared neuroanatomical indices and three papers which compared neurochemical indices. The neuroanatomical indices differentiating agitation and aggression included changes in brain perfusion, sizes of brain areas, distribution of neurofibrillary tangles, and white matter changes. The neurochemical indices differentiating agitation and aggression included relationships with neurotransmitter variables and the cell count in the locus coeruleus. Conclusion Despite the small number of papers and some methodological problems, the presented information clearly indicates that aggression and agitation are two distinct unrelated syndromes in persons with dementia.

Cortical pattern of reduced perfusion in hearing loss revealed by ASL-MRI.

Age-related hearing loss (HL) can be related to brain dysfunction or structural damage and may result in cerebral metabolic/perfusion abnormalities. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows investigating noninvasively brain perfusion changes. Pseudocontinuous ASL and T1-weighted MRI (at 3 T) and neuropsychological testing (Montreal Cognitive Assessment) were performed in 31 HL (age range = 47-77 years, mean age ± SD = 63.4 ± 8.4 years, pure-tone average [PTA] HL > 50 dB) and 28 normal hearing (NH; age range = 48-78 years, mean age ± SD = 59.7 ± 7.4 years) subjects. Cerebral blood flow (CBF) and gray matter volume (GMV) were analyzed in the cortical volume to assess perfusion and structural group differences. Two HL subjects showing cognitive impairment were excluded from group comparisons. No significant differences in either global or local atrophy were detected between groups but the HL group exhibited significant regional effects of reduced perfusion within the bilateral primary auditory cortex, with maximal CBF difference (-17.2%) in the right lateral Heschl's gyrus. For the whole sample of HL and NH subjects (n = 59 = 31 HL + 28 NH), the regional CBF was correlated positively to the regional GMV (p = 0.020). In HL subjects (n = 31), the regional CBF was correlated negatively to the audiogram steepness (frequency range: 2-4 kHz, right ear: p = 0.022, left ear: p = 0.015). The observed cortical pattern of perfusion reduction suggests that neuronal metabolism can be related to HL before the recognition of brain structural damage. This also illustrates the potential of ASL-MRI to contribute early functional markers of reduced central processing associated with HL.

High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling.

Exposure to hypobaric hypoxia at high altitude (above 2500 m asl) causes cognitive impairment, mostly attributed to changes in brain perfusion and consequently neuronal death. Enriched environment and voluntary exercise has been shown to improve cognitive function, to enhance brain microvasculature and neurogenesis, and to be neuroprotective. Here we show that high-altitude exposure (3540 m asl) of Long Evans rats during early adulthood (P48–P59) increases brain microvasculature and neurogenesis but impairs spatial and visual memory along with an increase in neuronal apoptosis. We tested whether enriched environment including a running wheel for voluntary exercise (EE) can prevent cognitive impairment at high-altitude and whether apoptosis is prevented. We found that EE retained spatial and visual memory at high altitude, and prevented neuronal apoptosis. Further, we tested whether vascular endothelial growth factor (VEGF) signaling is required for the EE-mediated recovery of spatial and visual memory and the reduction in apoptosis. Pharmacological inhibition of VEGF signaling by oral application of a tyrosine kinase inhibitor (Vandetanib) prevented the recovery of spatial and visual memory in animals housed in EE, along with an increase in apoptosis and a reduction in neurogenesis. Surprisingly, inhibition of VEGF signaling also caused impairment in spatial memory in EE-housed animals reared at low altitude, affecting mainly dentate gyrus microvasculature but not neurogenesis. We conclude that EE-mediated VEGF signaling is neuroprotective and essential for the maintenance of cognition and neurogenesis during high-altitude exposure, and for the maintenance of spatial memory at low altitude. Finally, our data also underlines the potential risk of cognitive impairment and disturbed high altitude adaption from the use of VEGF-signaling inhibitors for therapeutic purposes.

Changes in Brain Perfusion in Patients with Unilateral Lower-limb Paresis, before and after Training on a Pedaling Wheelchair: A Feasibility Study

Changes in Brain Perfusion in Patients with Unilateral Lower-limb Paresis, before and after Training on a Pedaling Wheelchair: A Feasibility Study

Changes in brain perfusion in successive arterial spin labeling MRI scans in neonates with hypoxic-ischemic encephalopathy.

The primary objective of this study was to evaluate changes in cerebral blood flow (CBF) using arterial spin labeling MRI between day 4 of life (DOL4) and day 11 of life (DOL11) in neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. The secondary objectives were to compare CBF values between the different regions of interest (ROIs) and between infants with ischemic lesions on MRI and infants with normal MRI findings.We prospectively included all consecutive neonates with HIE admitted to the neonatal intensive care unit of our institution who were eligible for therapeutic hypothermia. Each neonate systematically underwent two MRI examinations as close as possible to day 4 (early MRI) and day 11 (late MRI) of life. A custom processing pipeline of morphological and perfusion imaging data adapted to neonates was developed to perform automated ROI analysis.Twenty-eight neonates were included in the study between April 2015 and December 2017. There were 16 boys and 12 girls. Statistical analysis was finally performed on 37 MRIs, 17 early MRIs and 20 late MRIs. Eleven neonates had both early and late MRIs of good quality available. Eight out of 17 neonates (47%) had an abnormal on late MRI as performed and 7/20 neonates (35%) had an abnormal late MRI. CBF values in the basal ganglia and thalami (BGT) and temporal lobes were significantly higher on DOL4 than on DOL11. There were no significant differences between DOL4 and DOL11 for the other ROIs. CBF values were significantly higher in the BGT vs. the cortical GM, on both DOL4 and DOL11. On DOL4, the CBF was significantly higher in the cortical GM, the BGT, and the frontal and parietal lobes in subjects with an abnormal MRI compared to those with a normal MRI. On DOL11, CBF values in each ROI were not significantly different between the normal MRI group and the abnormal MRI group, except for the temporal lobes.This article proposes an innovative processing pipeline for morphological and ASL data suited to neonates that enable automated segmentation to obtain CBF values over ROIs. We evaluate CBF on two successive scans within the first 15 days of life in the same subjects. ASL imaging in asphyxiated neonates seems more relevant when used relatively early, in the first days of life. The correlation of intra-subject changes in cerebral perfusion between early and late MRI with neurodevelopmental outcome warrants investigation in a larger cohort, to determine whether the CBF pattern change can provide prognostic information beyond that provided by visible structural abnormalities on conventional MRI.