Reproducibility of arterial spin labeling cerebral blood flow image processing: A report of the ISMRM open science initiative for perfusion imaging (OSIPI) and the ASL MRI challenge.

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation.

INTRODUCTION AND OBJECTIVES: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.

Measurement of resistance-area product by transcranial Doppler: An alternative tool for cognitive screening in hypertensive on drug treatment?

Introduction: Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. Methods: Participants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. Results: Patients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). Conclusion: RAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

Exercise Reshapes the Brain: Molecular, Cellular, and Structural Changes Associated with Cognitive Improvements.

Physical exercise is well known as a non-pharmacological and holistic therapy believed to prevent and mitigate numerous neurological conditions and alleviate ageing-related cognitive decline. To do so, exercise affects the central nervous system (CNS) at different levels. It changes brain physiology and structure, promoting cognitive improvements, which ultimately improves quality of life. Most of these effects are mediated by neurotrophins release, enhanced adult hippocampal neurogenesis, attenuation of neuroinflammation, modulation of cerebral blood flow, and structural reorganisation, besides to promote social interaction with beneficial cognitive outcomes. In this review, we discuss, based on experimental and human research, how exercise impacts the brain structure and function and how these changes contribute to cognitive improvements. Understanding the mechanisms by which exercise affects the brain is essential to understand the brain plasticity following exercise, guiding therapeutic approaches to improve the quality of life, especially in obesity, ageing, neurodegenerative disorders, and following traumatic brain injury.

Dantrolene Significantly Improves Cerebral Blood Flow in a Rat Model of Hemorrhagic Vasospasms.

INTRODUCTION: A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg and 2 mg/kg) on MCA blood flow velocity (BFV) 7 days after the induction of CVSPs. METHODS: Vasospasms were induced by bathing the left common carotid artery with autologous whole blood. Age-matched sham rats were used as controls. BFV, mean arterial pressure (MAP), and heart rate (HR) were measured with a PeriFlux 5000 Laser Doppler System, and a CODA non-invasive blood pressure system, before and after administering the drugs. Morphometric evaluations were also performed to assess vascular alterations. RESULTS: BFV was reduced by 37% with dantrolene alone (n = 6, p ≤ 0.05) and by 27% with 2 mg/kg nimodipine (n = 6, p < 0.05), while it was not affected by 1 mg/kg nimodipine. The combination of 1 mg/kg nimodipine with dantrolene, however, decreased BFV by 35% (from 435.70 ± 21.53 to 284.30 ± 23.13 perfusion units, n = 7, p ≤ 0.05). A similar reduction (31%) was obtained with dantrolene and 2 mg/kg nimodipine (from 536.00 ± 32.61 to 367.80 ± 40.93 perfusion units, n = 6, p ≤ 0.05). Neither MAP nor HR was affected by dantrolene or nimodipine alone. The combination of dantrolene with 2 mg/kg nimodipine, however, decreased MAP and increased HR. Furthermore, 7 days after the induction of vasospasms, lumen area of the left common carotid artery decreased, whereas media thickness and the wall-to-lumen ratio increased when compared to contralateral controls. The latter finding suggests that vascular remodeling was present at this stage. CONCLUSION: Altogether, our results indicate that 2.5 mg/kg dantrolene significantly reduces BFV in the MCA without altering systemic hemodynamic parameters to a similar extent than the highest dose of nimodipine or the combination of dantrolene and the lowest dose of nimodipine. Therefore, dantrolene may provide a promising alternative to lower the risk, or partially revert, CVSP.

Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Abnormal cerebral microvascular perfusion and reactivity in female offspring of reduced uterine perfusion pressure (RUPP) mice model.

Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (-40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.

Orthostatic intolerance: a handicap of aging or physical deconditioning?

Despite several studies that have been investigated physical inactivity and age-related effects on orthostatic tolerance, impaired hemodynamics and postural balance responses to orthostatic stress are incorrectly attributed to aging or sedentarism alone. The isolated effects from aging and sedentarism should be investigated through comparative studies between senior athletes and age-matched controls, and physical activity assessments on aging follow-up studies. On the other hand, bed rest and space flight studies mimic accelerated physical inactivity or disuse, which is not the same physiological decline provoked by aging alone. Thus, the elementary question is: could orthostatic intolerance be attributed to aging or physical inactivity? The main purpose of this review is to provide an overview of possible mechanisms underlying orthostatic tolerance contrasting the paradigm of aging and/or physical inactivity. The key points of this review are the following: (1) to counterpoint all relevant literature on physiological aspects of orthostatic tolerance; (2) to explore the mechanistic aspects underneath the cerebrovascular, cardiorespiratory, and postural determinants of orthostatic tolerance; and (3) examine non-pharmacological interventions with the potential to counterbalance the physical inactivity and aging effects. To date, the orthostatic intolerance cannot be attributed exclusively with aging since physical inactivity plays an important role in postural balance, neurovascular and cardiorespiratory responses to orthostatic stress. These physiological determinates should be interpreted within an integrative approach of orthostatic tolerance, that considers the interdependence between physiological systems in a closed-loop model. Based on this multisystem approach, acute and chronic countermeasures may combat aging and sedentarism effects on orthostatic tolerance.

Brain Death Diagnosis in Primary Posterior Fossa Lesions.

Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. Objective: The aim of this study was to discuss the particularities of BD diagnosis in patients with posterior fossa lesions. Materials and Methods: The author made a systematic review of literature on this topic. Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions (i.e., cerebral hypoxia), the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions (i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum) may retain intracranial blood flow and EEG activity. In this article, I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also addressed Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to "Mother Talks" stimulus, rejecting the diagnosis of BD. Jahi McMath's MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find in some cases partial recovery of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder.

INTRODUCTION: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. METHODS: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. RESULTS: Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. CONCLUSION: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

Relationships Between Regional Cerebral Blood Flow and Neurocognitive Outcomes in Children and Adolescents With Congenital Heart Disease.

To identify regional cerebral blood flow (rCBF) alterations in children and adolescents with congenital heart disease (CHD) in relation to neurocognitive outcomes using a nonbiased data-driven approach. This is a prospective, observational study of children and adolescents with CHD without brain injury and healthy controls using pseudo-continuous arterial spin labeling (pCASL) MRI. Quantitative rCBF was compared between participants with CHD and healthy controls using a voxelwise data-driven method. Mediation analysis was then performed on a voxelwise basis, with the grouping variable as the independent variable, neurocognitive outcomes (from the NIH Toolbox Cognitive Battery) as the dependent variables, and rCBF as the mediator. After motion correction, a total of 80 studies were analyzable (27 for patients with CHD, 53 for controls). We found steeper age-related decline in rCBF among those with CHD compared to normal controls in the insula/ventromedial prefrontal regions (salience network) and the dorsal anterior cingulate and precuneus/posterior cingulate (default mode network), and posterior parietal/dorsolateral prefrontal (central executive network) (FWE-corrected P< 0.05). The reduced rCBF in the default mode/salience network was found to mediate poorer performance on an index of crystallized cognition from the NIH Toolbox Cognitive Battery in those with CHD compared to controls. In contrast, reduced rCBF in the central executive network/salience network mediated reduced deficits in fluid cognition among patients with CHD compared to controls. Regional cerebral blood flow alterations mediate domain-specific differences in cognitive performance in children and adolescents with CHD compared to healthy controls, independent of injury, and are likely related to brain and cognitive reserve mechanisms. Further research is needed to evaluate the potential of interventions in CHD targeting regional cerebral blood flow across lifespan.

Study of the relationship between regional cerebral saturation and pCO2 changes during mechanical ventilation to evaluate modifications in cerebral perfusion in a newborn piglet model

Near-infrared spectroscopy (NIRS) could be a useful continuous, non-invasive technique for monitoring the effect of partial pressure of carbon dioxide (PaCO2) fluctuations in the cerebral circulation during ventilation. The aim of this study was to examine the efficacy of NIRS to detect acute changes in cerebral blood flow following PaCO2 fluctuations after confirming the autoregulation physiology in piglets. Fourteen piglets (<72 h of life) were studied. Mean arterial blood pressure, oxygen saturation, pH, glycemia, hemoglobin, electrolytes, and temperature were monitored. Eight animals were used to evaluate brain autoregulation, assessing superior cava vein Doppler as a proxy of cerebral blood flow changing mean arterial blood pressure. Another 6 animals were used to assess hypercapnia generated by decreasing ventilatory settings and complementary CO2 through the ventilator circuit and hypocapnia due to increasing ventilatory settings. Cerebral blood flow was determined by jugular vein blood flow by Doppler and continuously monitored with NIRS. A decrease in PaCO2 was observed after hyperventilation (47.6±2.4 to 29.0±4.9 mmHg). An increase in PaCO2 was observed after hypoventilation (48.5±5.5 to 90.4±25.1 mmHg). A decrease in cerebral blood flow after hyperventilation (21.8±10.4 to 15.1±11.0 mL/min) and an increase after hypoventilation (23.4±8.4 to 38.3±10.5 mL/min) were detected by Doppler ultrasound. A significant correlation was found between cerebral oxygenation and Doppler-derived parameters of blood flow and PaCO2. Although cerebral NIRS monitoring is mainly used to detect changes in regional brain oxygenation, modifications in cerebral blood flow following experimental PaCO2 changes were detected in newborn piglets when no other important variables were modified.

Connectivity and Patterns of Regional Cerebral Blood Flow, Cerebral Glucose Uptake, and Aß-Amyloid Deposition in Alzheimer's Disease (Early and Late-Onset) Compared to Normal Ageing.

PURPOSE: The aim of this study was to investigate the differences in early (EOAD) and late (LOAD) onset of Alzheimer´s disease, as well as glucose uptake, regional cerebral blood flow (R1), amyloid depositions, and functional brain connectivity between normal young (YC) and Old Controls (OC). METHODOLOGY: The study included 22 YC (37 ± 5 y), 22 OC (73 ± 5.9 y), 18 patients with EOAD (63 ± 9.5 y), and 18 with LOAD (70.6 ± 7.1 y). Patients underwent FDG and PIB PET/CT. R1 images were obtained from the compartmental analysis of the dynamic PIB acquisitions. Images were analyzed by a voxel-wise and a VOI-based approach. Functional connectivity was studied from the R1 and glucose uptake images. RESULTS: OC had a significant reduction of R1 and glucose uptake compared to YC, predominantly at the dorsolateral and mesial frontal cortex. EOAD and LOAD vs. OC showed a decreased R1 and glucose uptake at the posterior parietal cortex, precuneus, and posterior cingulum. EOAD vs. LOAD showed a reduction in glucose uptake and R1 at the occipital and parietal cortex and an increased at the mesial frontal and temporal cortex. There was a mild increase in an amyloid deposition at the frontal cortex in LOAD vs. EOAD. YC presented higher connectivity than OC in R1 but lower connectivity considering glucose uptake. Moreover, EOAD and LOAD showed a decreased connectivity compared to controls that were more pronounced in glucose uptake than R1. CONCLUSION: Our results demonstrated differences in amyloid deposition and functional imaging between groups and a differential pattern of functional connectivity in R1 and glucose uptake in each clinical condition. These findings provide new insights into the pathophysiological processes of AD and may have an impact on patient diagnostic evaluation.

Elevated cerebral perfusion and preserved cognition in elite Brazilian Jiu-Jitsu athletes: Evidence for neuroprotection.

Brazilian Jiu-Jitsu (BJJ) is a popular martial art that exposes participants to recurrent intermittent asphyxiation due to controlled application of neck chokes. To what extent the sport impacts the regulation of cerebral blood flow (CBF) and cognition has not been examined. This study compared eleven elite Brazilian Jiu-Jitsu athletes (aged 30 ± 8 y) who trained 12 ± 6 hours/week for 8 ± 4 years against eleven cardiorespiratory fitness (CRF)- and age-matched controls. Internal carotid (ICA) and vertebral artery (VA) blood flow were measured via duplex ultrasound to determine global cerebral blood flow (gCBF). Mild cognitive impairment and sub-domains of memory, attention/concentration/visual motor coordination, and executive function were determined by psychometric testing. There was no evidence of mild cognitive impairment in the athletes, and cognitive function was comparable between groups (all p > 0.05). In contrast, resting gCBF was selectively elevated in the athletes (741 ± 186 mL∙min-1 vs. 573 ± 166 mL∙min-1 , p = 0.037) due to combined differences in ICA (+65 mL∙min-1 , p = 0.079) and VA (+19 mL∙min-1 , p = 0.277) flow. In conclusion, the sustained elevation in resting cerebral perfusion provides preliminary evidence for adaptive neuroprotection that is independent of CRF and likely mediated by choke-induced cerebral preconditioning and/or lifelong exposure to BJJ-specific high-intensity interval training.

Improvement in neurological outcome and brain hemodynamics after late cranioplasty.

BACKGROUND: Early cranioplasty has been encouraged after decompressive craniectomy (DC), aiming to reduce consequences of atmospheric pressure over the opened skull. However, this practice may not be often available in low-middle-income countries (LMICs). We evaluated clinical improvement, hemodynamic changes in each hemisphere, and the hemodynamic balance between hemispheres after late cranioplasty in a LMIC, as the institution's routine resources allowed. METHODS: Prospective cohort study included patients with bone defects after DC evaluated with perfusion tomography (PCT) and transcranial Doppler (TCD) and performed neurological examinations with prognostic scales (mRS, MMSE, and Barthel Index) before and 6 months after surgery. RESULTS: A final sample of 26 patients was analyzed. Satisfactory improvement of neurological outcome was observed, as well as significant improvement in the mRS (p = 0.005), MMSE (p < 0.001), and Barthel Index (p = 0.002). Outpatient waiting time for cranioplasty was 15.23 (SD 17.66) months. PCT showed a significant decrease in the mean transit time (MTT) and cerebral blood volume (CBV) only on the operated side. Although most previous studies have shown an increase in cerebral blood flow (CBF), we noticed a slight and nonsignificant decrease, despite a significant increase in the middle cerebral artery flow velocity in both hemispheres on TCD. There was a moderate correlation between the MTT and contralateral muscle strength (r = - 0.4; p = 0.034), as well as between TCD and neurological outcomes ipsilateral (MMSE; r = 0.54, p = 0.03) and contralateral (MRS; p = 0.031, r = - 0.48) to the operated side. CONCLUSION: Even 1 year after DC, cranioplasty may improve cerebral perfusion and neurological outcomes and should be encouraged.

Reactive oxygen species play a modulatory role in the hyperventilatory response to poikilocapnic hyperoxia in humans.

KEY POINTS: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2 -[H+ ] washout-induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia-induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2 -[H+ ] washout. ABSTRACT: The hypothetical mechanism for the increase in ventilation ( V̇E ) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2 -[H+ ] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX-evoked increase in V̇E , 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. V̇E , arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2 ) and CO2 (PCO2 ), pH, oxidant (8-isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8-isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8-isoprostane and attenuated both the reduction in CBF and the HX-induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans-cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2 , which, in turn, seems to be evoked by the excessive ROS production/accumulation.

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.

CAAos platform: an integrated platform for analysis of cerebral hemodynamics data.

Objective.The purpose of this article is to introduce readers to the concept and structure of the CAAos (CerebralAutoregulationAssessmentOpenSource) platform, and provide evidence of its functionality.Approach.The CAAos platform is a new open-source software research tool, developed in Python 3 language, that combines existing and novel methods for interactive visual inspection, batch processing and analysis of multichannel records. The platform is scalable, allowing for the customization and inclusion of new tools.Main results.Currently, the CAAos platform is composed of two main modules, preprocessing (containing artefact removal, filtering and signal beat to beat extraction tools) and cerebral autoregulation (CA) analysis modules. Two methods for assessing CA have been implemented into the CAAos platform: transfer function analysis (TFA) and the autoregulation index (ARI). In order to provide validation of the TFA and ARI estimates derived from the CAAos platform, the results were compared with those derived from two other algorithms. Validation was performed using data from 28 participants, corresponding to 13 acute ischemic stroke patients and 13 age- and sex-matched control subjects. Agreement between estimates was assessed by intraclass correlation coefficient and Bland-Altman analysis. No significant statistical difference between the algorithms was found. Moreover, there was an excellent correspondence between the curves of all parameters analysed, with the intraclass correlation coefficient ranging from 0.98 (95%CI 0.976-0.999) to 1.00 (95%CI 1 -1). The mean differences revealed a very small magnitude bias indicating an excellent agreement between the estimates.Significance.As open-source software, the source code for the software is freely available for noncommercial use, reducing barriers to performing CA analysis, allowing inspection of the inner-workings of the algorithms, and facilitating networked activities with common standards. The CAAos platform is a tailored software solution for the scientific community in the cerebral hemodynamic field and contributes to the increasing use and reproducibility of CA assessment.