Alterations In Cerebral Blood Flow Research Articles

Cerebral blood flow alterations specific to freezing of gait in Parkinson's disease.

Freezing of gait (FOG) have been associated with deficits in the cortico-basal ganglia-thalamic network. However, the resting-state cerebral blood flow (CBF) alterations specific to FOG in Parkinson's disease (PD) remain unknown. In total, sixty PD individuals, including 30 PD with FOG (PD-FOG) and 30 PD without FOG (PD-NFOG), and 30 healthy controls (HC) underwent arterial spin labeling magnetic resonance image. The CBF were voxel-wise compared among the three groups and validated in a different cohort of PD-FOG and PD-NFOG. The results revealed that patients with PD-FOG had increased CBF in bilateral thalamus and the left caudate nucleus and decreased CBF in the left inferior parietal cortex compared to patients with PD-NFOG. The inter-group differences of CBF between PD-FOG and PD-NFOG was confirmed in a different cohort in the validation analysis. Moreover, the CBF in left caudate nucleus was positively correlated with severity of FOG in PD-FOG patients. Perfusion alterations in both cortical and subcortical regions in the cortico-basal ganglia-thalamic network are related to the development of FOG in PD patients.

Perilesional Perfusion in Chronic Stroke-Induced Aphasia and Its Response to Behavioral Treatment Interventions.

Stroke-induced alterations in cerebral blood flow (perfusion) may contribute to functional language impairments in chronic aphasia, particularly in perilesional tissue. Abnormal perfusion in this region may also serve as a biomarker for predicting functional improvements with behavioral treatment interventions. Using pseudo-continuous arterial spin labeling in magnetic resonance imaging (MRI), we examined perfusion in chronic aphasia, in perilesional rings in the left hemisphere and their right hemisphere homologues. In the left hemisphere we found a gradient pattern of decreasing perfusion closer to the lesion. The opposite pattern was found in the right hemisphere, with significantly increased perfusion close to the lesion homologue. Perfusion was also increased in the right hemisphere lesion homologue region relative to the surrounding tissue. We next examined changes in perfusion in two groups: one group who underwent MRI scanning before and after three months of a behavioral treatment intervention that led to significant language gains, and a second group who was scanned twice at a three-month interval without a treatment intervention. For both groups, there was no difference in perfusion over time in either the left or the right hemisphere. Moreover, within the treatment group pre-treatment perfusion scores did not predict treatment response; neither did pre-treatment perfusion predict post-treatment language performance. These results indicate that perfusion is chronically abnormal in both hemispheres, but chronically abnormal perfusion did not change in response to our behavioral treatment interventions, and did not predict responsiveness to language treatment.

A dual potassium channelopathy underlies small vessel disease of the brain in a mouse model of Alzheimer's Disease

Mounting clinical and basic evidence has suggested that cerebral microcirculatory dysfunction is key to the pathogenesis of Alzheimer’s disease (AD), thus posing a potential new therapeutic target for AD treatment. However, despite observations of altered cerebral blood flow and autoregulatory capacity in AD patients, the underlying pathogenic mechanisms behind these defects are currently unknown. Here we present the first detailed study in to vascular ion channel function in the APP23 mouse model of AD. This model has a seven‐fold increase in amyloid precursor protein leading to substantial amyloid‐β plaque accumulation within the brain, as is described in AD patients. Using a range of physiological techniques; mainly pressure myography, patch clamp electrophysiology and high‐speed spinning disc confocal microscopy, we show that attenuation of large conductance calcium–activated potassium (BK) channel function in this model, due to a reduced frequency of calcium sparks, is responsible for the reduction in cerebral blood flow described. Further investigation into the role of amyloid‐β 1‐40, in particular, showed that vessels exposed to the peptide for 30 minutes exhibited significantly reduced BK channel function at both the cellular and vascular level. However, disparate from the APP23 mouse model, acute exposure to amyloid‐β 1‐40 resulted in an increase in calcium waves. Both a decrease in calcium sparks (as seen in the APP23 model) and an increase in calcium waves (as seen with acute application of the amyloid‐β 1‐40 peptide) results in contraction of cerebral arteries and a subsequent reduction of cerebral blood flow. The data directs future research in to preventative strategies that may help to stop alterations in calcium event initiation, restore microvasculature function and promote a healthy brain environment to limit disease progression in AD patients.

Altered Coupling of Cerebral Blood Flow and Functional Connectivity Strength in First-Episode Schizophrenia Patients With Auditory Verbal Hallucinations.

ObjectiveAuditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia with AVHs, alterations in resting-state cerebral blood flow (CBF) and functional connectivity have been described. However, the neurovascular coupling alterations specific to first-episode drug-naïve schizophrenia (FES) patients with AVHs remain unknown.MethodsResting-state functional MRI and arterial spin labeling (ASL) was performed on 46 first-episode drug-naïve schizophrenia (FES) patients with AVHs (AVH), 39 FES drug-naïve schizophrenia patients without AVHs (NAVH), and 48 healthy controls (HC). Then we compared the correlation between the CBF and functional connection strength (FCS) of the entire gray matter between the three groups, as well as the CBF/FCS ratio of each voxel. Correlation analyses were performed on significant results between schizophrenia patients and clinical measures scale.ResultsThe CBF/FCS ratio was reduced in the cognitive and emotional brain regions in both the AVH and NAVH groups, primarily in the crus I/II, vermis VI/VII, and cerebellum VI. In the AVH group compared with the HC group, the CBF/FCS ratio was higher in auditory perception and language-processing areas, primarily the left superior and middle temporal gyrus (STG/MTG). The CBF/FCS ratio in the left STG and left MTG positively correlates with the score of the Auditory Hallucination Rating Scale in AVH patients.ConclusionThese findings point to the difference in neurovascular coupling failure between AVH and NAVH patients. The dysfunction of the forward model based on the predictive and computing role of the cerebellum may increase the excitability in the auditory cortex, which may help to understand the neuropathological mechanism of AVHs.

Repetitive Transcranial Magnetic Stimulation Induces Quantified Functional and Structural Changes in Subcortical Stroke: A Combined Arterial Spin Labeling Perfusion and Diffusion Tensor Imaging Study.

PurposeTo explore the changes of cerebral blood flow (CBF) and fractional anisotropy (FA) in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation (rTMS) treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level.Materials and MethodsIn total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls (HCs) were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales.ResultsAfter rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex (CPC) loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment (FMA) scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract (CST). The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus.ConclusionOur results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST.

Cerebral Blood Flow and its Connectivity Deficits in Patients With Lung Cancer After Chemotherapy.

Purpose: This study was performed to investigate the regional cerebral blood flow (CBF) and CBF connectivity in the chemotherapy-induced cognitive impairment of patients with lung cancer by using arterial spin labeling. Methods: Pseudocontinuous arterial spin labeling perfusion magnetic resonance imaging and neuropsychological tests were performed for 21 patients with non-small cell lung cancer who had received chemotherapy CT (+) and 25 non-small cell lung cancer patients who need chemotherapy but did not yet received CT (-). The CT (+) group previously received platinum-based therapy for 3 months to 6 months (the time from their first chemotherapy to the MRI scan). Group comparisons were performed in the regional normalized CBF and CBF connectivity, and the relationship between the regional normalized CBF and cognitive impairment were detected. Results: The CT (+) group exhibited higher CBF in the left insula, right caudate, right superior occipital gyrus, left superior temporal gyrus (STG), and right middle frontal gyrus (MFG). MoCA scores as well as the memory scores were negatively correlated with the increased CBF in the right MFG (r = −0.492, p = 0.023; r = −0.497, p = 0.022). Alterations in the CBF connectivity were detected only in the CT (+) group between the following: right MFG and the right precentral gyrus; the right caudate and the right lingual gyrus; right caudate and right precuneus; left STG and the bilateral MFG; and the left STG and the right middle cingulum. Conclusion: These findings indicated that chemotherapy is associated with abnormalities in the CBF and connectivity alterations, which may contribute to the cognitive impairment in patients with lung cancer.

Stage-Dependent Cerebral Blood Flow and Leukoaraiosis Couplings in Subcortical Ischemic Vascular Disease and Alzheimer's Disease.

Background: Alzheimer’s disease (AD) and subcortical ischemic vascular disease (SIVD) have both been associated with white matter hyperintensities (WMHs) and altered cerebral blood flow (CBF) although the etiology of AD is still unclear.Objective: To test the hypothesis that CBF and WMHs have differential effects on cognition and that the relationship between CBF and WMHs changes with the subtypes and stages of dementia.Methods: Forty-two patients with SIVD, 50 patients with clinically-diagnosed AD, and 30 cognitively-normal subjects were included. Based on the Clinical Dementia Rating (CDR), the patients were dichotomized into early-stage (CDR = 0.5) and late-stage (CDR = 1 or 2) groups. CBF and WMH metrics were derived from magnetic resonance imaging and correlated with cognition.Results: Hierarchical linear regression revealed that CBF metrics had distinct contribution to global cognition, memory, and attention, whereas WMH metrics had distinct contribution to executive function (all p < 0.05). In SIVD, the WMHs in frontotemporal areas correlated with the CBF in bilateral thalami at the early stage; the correlation then became between the WMHs in basal ganglia and the CBF in frontotemporal areas at the late stage. A similar corticosubcortical coupling was observed in AD but involved fewer areas.Conclusion: A stage-dependent coupling between CBF and WMHs was identified in AD and SIVD, where the extent of cortical WMHs correlated with subcortical CBF for CDR = 0.5, whereas the extent of subcortical WMHs correlated with cortical CBF for CDR = 1–2.

The Association between Mean Arterial Pressure, Central Venous Pressure, Cerebral Perfusion Pressure, Lung Oxygenation, and Glasgow Coma Scale in Sepsis Patients in the Intensive Care Unit

BACKGROUND: Sepsis is the most frequent condition encountered in the intensive care unit (ICU). One of the neurological features of sepsis is sepsis-associated encephalopathy (SAE). The exact pathophysiology of SAE remains unclear. Many factors have been linked to SAE, such as hypotension, hypoxemia, and other metabolic abnormalities. However, alteration of cerebral blood flow is thought to be the main culprit behind SAE. AIM: This study aims to evaluate and find correlations between mean arterial pressure (MAP), central venous pressure (CVP), cerebral perfusion pressure (CPP), PaO2/FiO2 (PF) ratio, Glasgow Coma Scale (GCS), and level of consciousness. METHODS: A cross-sectional study was conducted from March 2020 to October 2020 in the ICU of H. Adam Malik Central Hospital, Medan, Indonesia. Patients over 18 years old with sepsis were included in this study. We recorded the demographic data, MAP, CVP, CPP, PF ratio, and GCS in the 1st h of ICU admission. The data were then analyzed to find the correlation between these parameters. RESULTS: The total subjects in this study were 62 patients, with an equal ratio of male-to-female. A quarter of the patients were intubated, affecting the GCS assessment. The median of GCS was 12. Most patients (46.8%) were determined to be somnolence. The mean age of the subjects is 54.84 ± 13.25 years old. There was no correlation between MAP, CVP, CPP, PF ratio, GCS, and level of consciousness in this study. CONCLUSIONS: Our study found no correlation between MAP, CVP, CPP, PF ratio, GCS, and level of consciousness in sepsis patients.

Alteration in cerebral blood flow, kynurenines with respect to mood profile in freshly recruited armed forces personnel

The present study is conducted to understand the association of mood profile with the kynurenine pathway (KP) metabolites, and cerebral hemodynamics in freshly recruited central armed forces personnel. Profile of Mood States questionnaire was utilized to assess mood profile, and Total Mood Disturbance (TMD) score was calculated. Transcranial Doppler was used to record blood flow velocity bilaterally of the middle cerebral artery. Chromatographic profile of the kynurenine metabolites was obtained in serum. Further, personnel were stratified according to sociodemographic variables (gender, age and diet) to observe the changes in their KP metabolic status. An activation of the kynurenic acid branch of the KP and the reduction in the mean blood flow velocity, and an increase in Gosling pulsatility index (PI) were observed in females having high TMD score. On gender comparative analysis, kynurenine metabolites of quinolinic acid branch and serotonin were significantly high in males. In males, with increase in age, a significant increase in the quinolinic acid branch of the KP was observed. Furthermore, a significant difference in level metabolites of the KP among the vegetarian and non-vegetarian groups was also observed. In conclusion we observed that increased TMD score was associated with cerebral hypoperfusion and higher vascular resistance along with activation of the KP. Our findings highlighted the importance of multi-facet brain function to showcase the close interaction of various dimensionalities and true picture of the assessee.

Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes

IntroductionImpaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased...

Cerebral Blood Flow Alterations in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Arterial Spin Labeling Studies

ObjectiveArterial spin labeling (ASL) studies have revealed inconsistent regional cerebral blood flow (CBF) alterations in patients with type 2 diabetes mellitus (T2DM). The aim of this systematic review and meta-analysis was to identify concordant regional CBF alterations in T2DM.MethodsA systematic review was conducted to the published literatures comparing cerebral perfusion between patients with T2DM and healthy controls using ASL. The seed-based d mapping (SDM) was further used to perform quantitative meta-analysis on voxel-based literatures and to estimate the regional CBF alterations in patients with T2DM. Metaregression was performed to explore the associations between clinical characteristics and cerebral perfusion alterations.ResultsA total of 13 studies with 14 reports were included in the systematic review and 7 studies with 7 reports were included in the quantitative meta-analysis. The qualitative review found widespread CBF reduction in cerebral lobes in T2DM. The meta-analysis found increased regional CBF in right supplementary motor area and decreased regional CBF in bilateral middle occipital gyrus, left caudate nucleus, right superior parietal gyrus, and left calcarine fissure/surrounding cortex in T2DM.ConclusionThe patterns of cerebral perfusion alterations, characterized by the decreased CBF in occipital and parietal lobes, might be the neuropathology of visual impairment and cognitive aging in T2DM.

Cerebral Blood Flow and Brain Functional Connectivity Changes in Older Adults Participating in a Mindfulness-Based Stress Reduction Program.

There is a growing interest in the potential beneficial effects of mindfulness meditation training in protecting against age-related physical, emotional, and cognitive decline. The current prospective, single-center, single-arm study investigated if functional magnetic resonance imaging-based changes in cerebral blood flow and brain functional connectivity could be observed in 11 elderly adults (mean age 79) after participation in a Mindfulness-Based Stress Reduction (MBSR) program. The results showed significantly (p < 0.05) altered cerebral blood flow and functional connectivity in the cingulate gyrus, limbic structures, and subregions of the temporal and frontal lobes, similar to findings of other meditation-related studies in younger populations. Furthermore, these changes were also associated with significant improvements in depression symptoms. This study suggests that the MBSR program can potentially modify cerebral blood flow and connectivity in this population.

Acute ischaemic stroke and its challenges for the intensivist.

Acute ischaemic stroke (AIS) is responsible for almost 90% of all strokes and is one of the leading causes of death and disability. Acute ischaemic stroke is caused by a critical alteration in focal cerebral blood flow (ischaemia) from a variety of causes, resulting in infarction. The primary cerebral injury due to AIS occurs in the first hours, therefore early reperfusion importantly impacts on patient outcome ('Time is brain' concept). Secondary cerebral damage progressively evolves over the following hours and days due to cerebral oedema, haemorrhagic transformation, and cerebral inflammation. Systemic complications, such as pneumonia, sepsis, and deep venous thrombosis, could also affect outcome. The risk of a recurrent ischaemic stroke is in particular high in the first days, which necessitate particular attention. The role of intensive care unit physicians is therefore to avoid or reduce the risk of secondary damage, especially in the areas where the brain is functionally impaired and 'at risk' of further injury. Therapeutic strategies therefore consist of restoration of blood flow and a bundle of medical, endovascular, and surgical strategies, which-when applied in a timely and consistent manner-can prevent secondary deterioration due to cerebral and systemic complications and recurrent stroke and improve short- and long-term outcomes. A multidisciplinary collaboration between neurosurgeons, interventional radiologists, neurologists, and intensivists is necessary to elaborate the best strategy for the treatment of these patients.

Respiratory physiology at high altitude and considerations for pediatric patients.

Over 150million people, including many children, live at high altitude (>2500m) with the majority residing in Asia and South America. With increases in elevation, the partial pressure of oxygen (pO2) is reduced, resulting in a hypobaric hypoxic environment. Fortunately, humans have evolved adaptive processes which serve to acclimate the body to such conditions. These mechanisms, occurring along a specific time course, result in tachypnea, tachycardia, diuresis, and hematopoiesis, and a shift in the oxygen dissociation curve favoring an increased affinity for oxygen. These, along with other physiological effects, including increased pulmonary vascular resistance, alterations in cerebral blood flow, and changes in sensitivity to opioids, must be considered when administering anesthesia at high altitudes. Susceptible individuals or those who ascend too quickly may outpace the body's ability to acclimate resulting in one or more forms of high-altitude sickness ranging from the milder acute mountain sickness to the more serious conditions of high-altitude pulmonary edema and cerebral edema, either of which can be life-threatening if not promptly recognized and treated. Since the adaptive mechanisms for acclimatization greatly affect the cardiopulmonary systems, patients with underlying health issues such as sleep apnea, congenital heart disease, and asthma may have susceptibilities and warrant special consideration. Clinicians should have an understanding of the physiologic adaptations, anesthetic considerations, and special concerns in these populations in order to offer the best care possible.

Perfusion heterogeneity of cerebral small vessel disease revealed via arterial spin labeling MRI and machine learning

Cerebral small vessel disease (CSVD) is associated with altered cerebral perfusion. However, global and regional cerebral blood flow (CBF) are highly heterogeneous across CSVD patients. The aim of this study was to identify subtypes of CSVD with different CBF patterns using an advanced machine learning approach. 121 CSVD patients and 53 healthy controls received arterial spin label MRI, T1 structural MRI and clinical measurements. Regional CBF were used to identify distinct perfusion subtypes of CSVD via a semi-supervised machine learning algorithm. Statistical analyses were used to explore alterations in CBF, clinical measures, gray and white matter volume between healthy controls and different subtypes of CSVD. Correlation analysis was used to assess the association between clinical measures and altered CBF in each CSVD subtype. Three subtypes of CSVD with distinct CBF patterns were found. Subtype 1 showed decreased CBF in the temporal lobe and increased CBF in the parietal and occipital lobe. Subtype 2 exhibited decreased CBF in the right hemisphere of the brain, and increased CBF in the left cerebrum. Subtype 3 demonstrated decreased CBF in the posterior part of the brain, and increased CBF in anterior part of the brain. The three subtypes also differed significantly in gender (p = 0.005), the proportion of subjects with lacune (p = 0.002), with periventricular white matter hyperintensity (p = 0.043), and CSVD burden score (p = 0.048). In subtype 3, it was found that widespread decreased CBF was correlated with total CSVD burden score (r = -0.324, p = 0.029). Compared with healthy controls, the three CSVD subtypes also showed distinct volumetric patterns of white matter. The current results associate different subtypes with different clinical and imaging phenotypes, which can improve the understanding of brain perfusion alterations of CSVD and can facilitate precision diagnosis of CSVD.

Acupuncture Effects on Cerebral Blood Flow during Normoxia and Normobaric Hypoxia: Results from a Prospective Crossover Pilot Study

Cerebral blood flow (CBF) is significantly influenced by exposure to hypoxia, both hypobaric and normobaric. Alterations in cerebral blood flow can play a crucial role in the pathogenesis of acute mountain sickness (AMS) and its symptoms, especially headache, dizziness, and nausea. Acupuncture has been proven to be effective in treating some cerebrovascular disorders and PC6 Nei Guan stimulation seems to enhance cerebral blood flow. Therefore, we have hypothesized that PC6 Nei Guan stimulation could affect CBF in acute hypoxia and could be used to contrast AMS symptoms. We evaluated blood flow in the middle cerebral artery (MCA) in normoxia, after 15 min in normobaric hypoxia (fraction of inspired oxygen (FiO2) 14%, corresponding to 3600 m a.s.l.) in basal conditions, and after PC6 Nei Guan stimulation, both by needle and by pressure. No comparisons with other acupuncture points and sham acupuncture were done. PC6 stimulation seemed to counteract the effects of acute normobaric hypoxia on end-diastolic velocity (EDV) in MCA, especially after acupuncture, and significantly reduced systolic and diastolic blood pressure. A rebalance of CBF could control some AMS symptoms, but further studies are necessary.

The relationship between blood‐brain barrier permeability and cerebral blood flow in cognitive impairment

AbstractBackgroundThe contribution of cerebral microvascular dysfunction to early cognitive impairment and dementia is increasingly recognized. Here we investigated cerebral blood flow (CBF) and blood–brain barrier (BBB) permeability in relation to early cognitive decline in APOE3‐homozygotes (ε3/ε3) and APOE4‐carriers (ε3/ε4; ε4/ε4).MethodA total of 237 participants underwent neuropsychological evaluations, venipuncture, and magnetic resonance imaging (MRI). The global Clinical Dementia Rating (CDR) was used to classify participants in cognitively unimpaired (CU, CDR=0) and mild cognitive impairment (CDR=0.5). APOE genotyping was performed via polymerase chain reaction‐based retention fragment length polymorphism analysis on DNA extracted from buffy coat. BBB permeability and CBF were estimated from dynamic contrast‐enhanced and 3D pseudo‐continuous arterial spin labeling (pCASL) MRI data, respectively, using in‐house pipelines. After excluding APOE2‐carriers and participants with CDR&gt;0.5, 143 participants (86 females [60.1%]) were included in the analysis. (Table 1)ResultStandardized CBF levels in grey matter (GM), hippocampus (HC), and parahippocampal gyrus (PHG) were not significantly different in APOE3‐homozygotes and APOE4‐carriers, after controlling for age and sex. (Figure 1) Our results of BBB permeability in 52 CU participants (27 APOE3‐homozygotes and 25 APOE4‐carriers) confirm a significantly higher BBB permeability in the HC of APOE4‐carriers compared with APOE3‐homozygotes (p&lt;0.001), as previously reported (Montagne et al., Nature, 2020), and show no relationship between BBB permeability and CBF. (Figure 2) In a subgroup of 46 participants (21 CU APOE3‐homozygotes, 18 CU APOE4‐carriers, and 7 APOE4‐carriers with CDR=0.5) who underwent a second MRI approximately 2 years after the first MRI, we observed a significant reduction (p=0.008) of CBF in APOE4‐carriers with mild cognitive impairment, but not in CU individuals.ConclusionAPOE4 is associated with higher BBB permeability in CU participants compared with APOE3‐homozygotes, but CBF is not different between the two genotypes. In the future, longitudinal data will be collected to confirm whether BBB breakdown precedes CBF alterations and to assess their relationship with cognitive decline, amyloid‐β and tau pathology.

Microenvironmental Variations After Blood-Brain Barrier Breakdown in Traumatic Brain Injury.

Traumatic brain injury (TBI) is linked to several pathologies. The blood-brain barrier (BBB) breakdown is considered to be one of the initial changes. Further, the microenvironmental alteration following TBI-induced BBB breakdown can be multi-scaled, constant, and dramatic. The microenvironmental variations after disruption of BBB includes several pathological changes, such as cerebral blood flow (CBF) alteration, brain edema, cerebral metabolism imbalances, and accumulation of inflammatory molecules. The modulation of the microenvironment presents attractive targets for TBI recovery, such as reducing toxic substances, inhibiting inflammation, and promoting neurogenesis. Herein, we briefly review the pathological alterations of the microenvironmental changes following BBB breakdown and outline potential interventions for TBI recovery based on microenvironmental modulation.

4D flow MRI hemodynamic biomarkers for cerebrovascular diseases.

Alterations in cerebral blood flow are common in several neurological diseases among the elderly including stroke, cerebral small vessel disease, vascular dementia, and Alzheimer's disease. 4D flow magnetic resonance imaging (MRI) is a relatively new technique to investigate cerebrovascular disease, and makes it possible to obtain time-resolved blood flow measurements of the entire cerebral arterial venous vasculature and can be used to derive a repertoire of hemodynamic biomarkers indicative of cerebrovascular health. The information that can be obtained from one single 4D flow MRI scan allows both the investigation of aberrant flow patterns at a focal location in the vasculature as well as estimations of brain-wide disturbances in blood flow. Such focal and global hemodynamic biomarkers show the potential of being sensitive to impending cerebrovascular disease and disease progression and can also become useful during planning and follow-up of interventions aiming to restore a normal cerebral circulation. Here, we describe 4D flow MRI approaches for analyzing the cerebral vasculature. We then survey key hemodynamic biomarkers that can be reliably assessed using the technique. Finally, we highlight cerebrovascular diseases where one or multiple hemodynamic biomarkers are of central interest.

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.