Cerebral Blood Flow Levels Research Articles

Construction and Application of Cerebral Functional Region-Based Cerebral Blood Flow Atlas Using Magnetic Resonance Imaging-Arterial Spin Labeling.

Cerebral conditions often require precise diagnosis and monitoring, necessitating advanced imaging techniques. Current modalities may not adequately detect early signs of reversible tissue damage, underlining the need for innovative diagnostic tools that can quantify changes in cerebral blood flow (CBF) with high specificity and sensitivity.This study integrates three-dimensional arterial spin labeling (3D-ASL) with structural MRI to develop comprehensive CBF atlases that cover all main functional regions of the brain. This innovative magnetic resonance imaging- arterial spin labeling (MRI-ASL) methodology provides a rapid and noninvasive means of quantifying region-specific CBF, offering a detailed view of CBF levels across different functional regions.The comparison between chronic cerebral ischemia (CCI) patients and healthy subjects revealed significantly diminished CBF across the cerebral functional regions in the constructed CBF atlases for the former. This approach not only allows for the efficient identification of CCI by analyzing concurrent decreases in CBF across critical areas relative to healthy distributions but also enables the tracking of treatment responses and rehabilitation progress through longitudinal CBF atlases.The CBF atlas developed using the MRI-ASL technique represents a novel advancement in the field of cerebral diagnostics and patient care. By comparing regional CBF levels against normative standards, this method enhances diagnostic capabilities, enabling clinicians to provide personalized care to patients with cerebral conditions.

Predictive value of TCCD and regional cerebral oxygen saturation for detecting early postoperative brain injury

ObjectiveThis study aims to analyze the risk factors for early postoperative brain injury in patients undergoing cardiovascular surgery and explore the predictive value of transcranial color Doppler (TCCD) and regional cerebral oxygen saturation (rSO2) for detecting early postoperative brain injury in cardiovascular surgery patients.MethodsA total of 55 patients undergoing cardiovascular surgery with cardiopulmonary bypass in Changzhou No.2 The People’s Hospital of Nanjing Medical University were included in this study. Neuron-specific enolase (NSE) concentration was measured 24 h after operation. Patients were divided into brain injury (NSE ≥ 16.3 ng/mL) and normal (0 < NSE < 16.3 ng/mL) groups according to the measured NSE concentration. The clinical outcomes between the two groups were compared, including decreased rSO2 and cerebral blood flow (as measured by TCCD) levels. The risk factors of early postoperative brain injury were analyzed by multivariate logistic regression analysis, and the significant variables were analyzed by receiver operating characteristic (ROC) analysis.ResultsA total of 50 patients were included in this study, with 20 patients in the brain injury group and 30 patients in the normal group. Cardiopulmonary bypass time (min) (107 ± 29 vs. 90 ± 28, P = 0.047) and aortic occlusion time (min) (111 (IQR 81–127) vs. 87 (IQR 72–116), P = 0.010) were significantly longer in the brain injury group than in the normal group. Patients in the brain injury group had greater decreased rSO2 (%) (27.0 ± 7.3 vs. 17.5 ± 6.1, P < 0.001) and cerebral blood flow (%) (44.9 (IQR 37.8–69.2) vs. 29.1 (IQR 12.0–48.2), P = 0.004) levels. Multivariate logistic regression analysis suggested that decreased rSO2 and cerebral blood flow levels, aortic occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury (P < 0.05). ROC analysis reported that the best cutoff values for predicting early postoperative brain injury were 21.4% and 37.4% for decreased rSO2 and cerebral blood flow levels, respectively (P < 0.05).ConclusionThe decreased rSO2 and cerebral blood flow levels, aorta occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury. TCCD and rSO2 could effectively monitor brain metabolism and cerebral blood flow and predict early postoperative brain injury.

Cerebral autoregulation, spreading depolarization, and implications for targeted therapy in brain injury and ischemia.

Cerebral autoregulation is an intrinsic myogenic response of cerebral vasculature that allows for preservation of stable cerebral blood flow levels in response to changing systemic blood pressure. It is effective across a broad range of blood pressure levels through precapillary vasoconstriction and dilation. Autoregulation is difficult todirectly measure and methods to indirectly ascertain cerebral autoregulation status inherently require certain assumptions. Patients with impaired cerebral autoregulation may be at risk of brain ischemia. One of the central mechanisms of ischemia in patients with metabolically compromised states is likely the triggering of spreading depolarization (SD) events and ultimately, terminal (or anoxic) depolarization. Cerebral autoregulation and SD are therefore linked when considering the risk of ischemia. In this scoping review, we will discuss the range of methods to measure cerebral autoregulation, their theoretical strengths and weaknesses, and the available clinical evidence to support their utility. We will then discuss the emerging link between impaired cerebral autoregulation and the occurrence of SD events. Such an approach offers the opportunity to better understand an individual patient's physiology and provide targeted treatments.

Dynamic cerebral blood flow assessment based on electromagnetic coupling sensing and image feature analysis.

Dynamic assessment of cerebral blood flow (CBF) is crucial for guiding personalized management and treatment strategies, and improving the prognosis of stroke. However, a safe, reliable, and effective method for dynamic CBF evaluation is currently lacking in clinical practice. In this study, we developed a CBF monitoring system utilizing electromagnetic coupling sensing (ECS). This system detects variations in brain conductivity and dielectric constant by identifying the resonant frequency (RF) in an equivalent circuit containing both magnetic induction and electrical coupling. We evaluated the performance of the system using a self-made physical model of blood vessel pulsation to test pulsatile CBF. Additionally, we recruited 29 healthy volunteers to monitor cerebral oxygen (CO), cerebral blood flow velocity (CBFV) data and RF data before and after caffeine consumption. We analyzed RF and CBFV trends during immediate responses to abnormal intracranial blood supply, induced by changes in vascular stiffness, and compared them with CO data. Furthermore, we explored a method of dynamically assessing the overall level of CBF by leveraging image feature analysis. Experimental testing substantiates that this system provides a detection range and depth enhanced by three to four times compared to conventional electromagnetic detection techniques, thereby comprehensively covering the principal intracranial blood supply areas. And the system effectively captures CBF responses under different intravascular pressure stimulations. In healthy volunteers, as cerebral vascular stiffness increases and CO decreases due to caffeine intake, the RF pulsation amplitude diminishes progressively. Upon extraction and selection of image features, widely used machine learning algorithms exhibit commendable performance in classifying overall CBF levels. These results highlight that our proposed methodology, predicated on ECS and image feature analysis, enables the capture of immediate responses of abnormal intracranial blood supply triggered by alterations in vascular stiffness. Moreover, it provides an accurate diagnosis of the overall CBF level under varying physiological conditions.

Abstract WP218: Risk Factors for Cerebral Aneurysms in Sickle Cell Disease

Introduction: Cerebral aneurysm frequency in sickle cell disease (SCD) is higher than in the general population. Specific risk factors explaining this difference have not been previously explored. We hypothesize that increased cerebral blood flow (CBF), low hemoglobin (Hb) levels, and documented risk factors for aneurysms in the general population would be associated with aneurysm development in SCD. Methods: Children and young adults with SCD defined as HbSS and HbSβ0 thalassemia were recruited from SCD clinics at an academic medical center and a community health clinic from 2014-2022 along with age and race-matched controls. Written consent and assent were required. Inclusion: ages 6-45 years, study MRI and MRA of the brain, risk factor data collected. MRAs were reviewed and aneurysms were confirmed by consensus of 2 neuroradiologists. CBF was assessed via MRI with pseudo-continuous arterial spin labeling. Results: The study population included 183 SCD participants, including 13 (7.1%) with aneurysms. The healthy control group included 77 participants, 3 (3.9%) of these participants had aneurysms, all women. In the SCD sample, 10 of 13 (76.9%) aneurysms occurred in males while 76 of 170 (44.7%) without aneurysms were male (p=0.025). In the aneurysm group, 3 of 13 (23.1%) were smokers versus 8 of 170 (4.7%) without aneurysms (p=0.035). In the SCD aneurysm group, median age was older, 30.9 years versus 17.2 years without aneurysm, (p&lt;0.001). Systolic blood pressure and Hb levels were not different in SCD participants with and without aneurysms, p=0.074 and p=0.358, respectively. However, SBP was 119.7±14.9 with aneurysms vs 113.2±12.3mmHg without aneurysms. Mean gray matter CBF for the SCD group with aneurysms was higher at 86.7± 25.9ml/100g/min compared to 80.8 ± 20.3ml/100g/min in the SCD group without aneurysms, though not significantly (p=0.325). Discussion: Increased CBF and low hemoglobin levels were not risk factors for cerebral aneurysms in SCD in this relatively small cohort. Like the general population, age and smoking are risk factors for aneurysm development in SCD. In contrast to the general population, male sex rather than female sex in SCD is an aneurysm risk factor. Based on these data, a larger consortium to study aneurysms in SCD is needed.

Neuroprotective action of hydroxybenzoic acid derivative with glycine (C40) in the middle cerebral artery occlusion in rats with chronic cerebral circulation insufficiency

The neuroprotective effect of a novel conjugate of hydroxybenzoic acid with glycine (C40) was investigated in a model of ischemic stroke in rats with chronic cerebral circulation insufficiency (CCCI). The study was conducted in two stages: first, CCCI was modeled by stenosing the common carotid arteries by 50 %, followed by a 60-minute middle cerebral artery occlusion (stroke) after 40 days. Compound C40 and the reference drug citicoline were administered for 10 days before stroke and for 3 days after. Further, neurological deficit (the Garcia and Combs D’Alecy scales), sensorimotor functions (Open Field test, Adhesive Removal test, and Rotarod test), cognitive impairments (Novel Object Recognition and Morris Water Maze tests), cerebral blood flow level, and endothelial function were evaluated. Animals receiving the test substances demonstrated a statistically significant reduction in neurological deficit, less pronounced motor coordination and sensorimotor function impairments, as well as fewer short-term and long-term memory deficits compared to the negative control group. The observed decrease in neurological deficit in the experimental groups was accompanied by improved endothelial function and increased cerebral blood flow. The neuroprotective effect of the novel hydroxybenzoic acid derivative with glycine (C40) was comparable to that of reference drug citicoline.

Abstract 17490: Impaired Cerebrovascular Oxygen Delivery, Reserve, and Metabolism in Adult Fontan Patients

Introduction: Patients with univentricular hearts undergo a three-stage surgical palliation, culminating in total caval-pulmonary connection (Fontan procedure), maximizing delivery of oxygenated blood to the systemic circulation. Prior brain research in this population has highlighted genetic predisposition, in-utero oxygen delivery, surgical insults, and pre-Fontan cyanosis as possible mechanisms of brain injury, but none have examined the impact of the Fontan repair on brain hemodynamics. Study Purpose: To determine the sufficiency of brain O 2 delivery, cerebrovascular reserve (CVR), brain O 2 extraction fraction (OEF), and cerebral metabolic rate of O 2 (CMRO 2 ) in adult Fontan patients, compared to permeability-surface area (PS) of blood brain barrier (BBB) integrity to water, and endothelin levels. Hypothesis: We hypothesized that brain O 2 delivery, CVR, PS, and CMRO 2 would be decreased in Fontan patients, proportional to endothelin levels, an established surrogate for low cardiac output. Methods: We have enrolled 35 Fontan patients (age 20.8 ± 2.5 years, 21M) and 24 control subjects (age 23.4 ± 4.8 years, 9M) to undergo brain MRI, excluding all subjects with known stroke, seizure, or genetic abnormalities. We collected total cerebral blood flow (CBF), OEF, CVR, and PS using 3T MRI. Results: Table 1 summarizes differences in O 2 delivery, CBF, OEF, CMRO 2 , CVR, PS, and endothelin levels in the study cohort. O 2 delivery, CBF, CVR, and CMRO 2 were decreased in Fontan patients; OEF and PS were not different. Endothelin was increased but uncorrelated with the brain metrics. CMRO 2 was correlated with PS (r 2 = 0.19, p&lt;0.001). Conclusion: Adult survivors of Fontan palliation have decreased brain O 2 delivery and reserve, without compensatory OEF increases, leading to lower CMRO 2 . Decreased CMRO 2 was associated with decreased PS, but not endothelin, suggesting microvascular dysfunction rather than low cardiac output as the fundamental etiology.

A - 128 Sex Differences in CBF in a Pediatric Sample of Depression: a SPECT Analysis.

The present study aims to determine whether there are differences in cerebral blood flow (CBF) levels in females versus males with depression. The data for this study was derived from an archival SPECT database. Participants in the female group (n = 140, Mage = 14.48) were like those in the male group (n = 241, Mage = 13.77). Multiple independent t-tests were performed between the female and male groups on the CBF levels in the left and right sides of the cerebellum, cingulum, frontal, occipital, parietal, and temporal lobes, and subcortical areas. CBF levels in males were higher than those of females in the following areas: the left and right sides of the cerebellum, and occipital lobe, the right side of the parietal lobe, and the temporal lobe. CBF levels in females were higher than those of males in the following areas: the left and right sides of the cingulum, the vermis, and the subcortical areas. While females had higher CBF in subcortical areas, the findings regarding higher CBF levels in males raise questions regarding prior literature which suggested that females have higher CBF than males in studies of depression subjects. These differences may be due to the differences in how males and females cope with depressive symptoms. Sex differences in CBF may suggest a contributing factor in the relationship between sex and responsiveness to antidepressant medication, ketamine treatment, and transcranial magnetic stimulation.

Improved cerebral blood flow and hippocampal blood flow in stroke-free patients after catheter ablation of atrial fibrillation.

Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR). A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements. Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02). SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months.

Dobutamine-induced alternations in cerebral blood flow of healthy adults: a 3D pseudocontinuous arterial spin labeling study

BackgroundIt is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics.MethodsForty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes.ResultsHR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P < 0.001, pixel level P < 0.05). Logistic regression showed that body mass index (BMI; odds ratio [OR] 5.80, 95% confidence interval [CI] 1.60–21.01, P = 0.008], resting SBP (OR 0.64, 95% CI 0.45–0.92, P = 0.014), and BA diameter (OR 11.04, 95% CI 1.05–116.53, P = 0.046) were significantly associated with frontal lobe CBF changes.ConclusionsDobutamine-induced stress significantly decreased CBF in the frontal lobe anterior circulation. Individuals with a high BMI and low SBP during the dobutamine stress test are more likely to have a stress-induced CBF decrease. Thus, attention should be paid to blood pressure, BMI, and cerebrovascular morphology of patients undergoing dobutamine stress echocardiography or those receiving intensive care or anesthesia.

Arterial spin labeling for moyamoya angiopathy: A preoperative and postoperative evaluation method.

Studies have shown that arterial spin labeling (ASL) effectively replaces traditional MRI perfusion imaging for detecting cerebral blood flow (CBF) in patients with Moyamoya angiopathy (MMA). However, there are few reports on the relationship between neovascularization and cerebral perfusion in patients with MMA. The aim of this study is to investigate the effects of neovascularization on cerebral perfusion with MMA after bypass surgery. We selected patients with MMA in the Department of Neurosurgery between September 2019 and August 2021 and enrolled them based on the inclusion and exclusion criteria. ASL imaging was used to monitor the baseline CBF level before surgery and determine the changes in cerebral vessels at postoperative 1 week and 6 months, respectively. The Alberta stroke grade, modified Rankin Scale (mRS), and digital subtraction angiography images were used to evaluate the effect of postoperative CBF status and prognosis. Ninety hemispheres from 51 patients were included in this study. There were no significant differences in the baseline data of the enrolled patients. At 1 week and 6 months post-surgery, the CBF state in the operation area was significantly changed compared with that at baseline (P < 0.05). The preoperative Alberta score (t = 2.714, P = 0.013) and preoperative mRS score (t = 6.678, P < 0.001) correlated with postoperative neovascularization. ASL is an effective method for detecting CBF and plays an important role in the long-term follow-up of patients with MMA. Combined cerebral revascularization significantly improves CBF in the operation area both in the short and long terms. Patients with lower preoperative Alberta scores and higher mRS scores were more likely to benefit from combined cerebral revascularization surgery. However, regardless of the type of patient, CBF reconstruction can effectively improve prognosis.

Associations between everyday activities and arterial spin labeling‐derived cerebral blood flow: A longitudinal study in community‐dwelling elderly volunteers

Cerebral blood flow (CBF) is critical for brain metabolism and function. Age-related changes in CBF are associated with increased risk of neurocognitive disorders and vascular events such as stroke. Identifying correlates and positive modifiers of age-related changes in CBF before the emergence of incipient clinical decline may inform public health advice and clinical practice. Former research has been inconclusive regarding the association between regular physical activity and CBF, and there is a lack of studies on the association between level of everyday activities and CBF, in older adults. To investigate these relationships, 118 healthy community-dwelling adults (65-89 years) underwent pseudo-continuous arterial spin labeling (ASL) MRI, neurocognitive, physical, and activity assessments at baseline. Eighty-six participants completed a follow-up ASL MRI, on average 506 (SD=113) days after the baseline scan. Cross-sectional analysis revealed credible evidence for positive associations between time spent on low intensity physical activity and CBF in multiple cortical and subcortical regions, time spent on moderate to vigorous intensity physical activity and accumbens CBF, participation in social activity and CBF in multiple cortical regions, and between reading and thalamic CBF, indicating higher regional CBF in more active adults. Longitudinal analysis revealed anecdotal evidence for an interaction between time and baseline level of gardening on occipital and parietal CBF, and baseline reading on pallidum CBF, indicating more change in CBF in adults with lower level of activity. The findings support that malleable lifestyle factors contribute to healthy brain aging, with relevance for public health guidelines.

Abstract Number ‐ 249: Differential Ischemic Vulnerability depicted by White Matter‐Sparing Infarction following Alteplase Recanalization

Introduction Gray and white matter possess different ischemic thresholds and therefore will undergo infarction at different rates of cerebral blood flow. We present a patient that presented with a large vessel occlusion and recanalized following alteplase administration within hours of symptom onset. Follow‐up imaging revealed a white matter‐sparing infarction, visually depicting the differential ischemic vulnerability between gray and white matter. Methods Case Report. Results An 83‐year‐old woman with a medical history of dementia, hypertension, and atrial fibrillation, not on anticoagulation due to recent gastrointestinal hemorrhage, presented with speech difficulty and right sided weakness. Her blood pressure was elevated at 170/86 and neurological exam demonstrated mixed aphasia, right homonymous hemianopia, left gaze deviation, and dense right hemiparesis with a National Institutes of Health Stroke Scale of 23. Non‐contrast CT of the head showed a hyperdense left terminal internal cerebral artery (ICA) and was otherwise unremarkable (Figure 1, A). CT angiography of the head and neck revealed an ICA “T” occlusion with no flow seen at the ICA terminus, the left anterior cerebral (A1) and middle cerebral (M1) segments (Figure 1, B). She was treated with intravenous alteplase 132 minutes from when she was last known normal. She was transferred to our comprehensive stroke center for mechanical thrombectomy, however, catheter angiography showed spontaneous recanalization of left ICA (Figure 1, C). Brain MRI the following day showed a white matter‐sparing infarction involving the left ICA territory (Figure 1, D‐F). She was discharged to rehab with moderate improvement in her aphasia and right hemiparesis. Conclusions This case visually depicts the differential ischemic vulnerability between gray and white matter since recanalization likely occurred at a cerebral blood flow level below the gray matter ischemic threshold while remaining above the white matter threshold. While pretreatment ischemic core volumes are inversely correlated with functional outcomes after recanalization of large vessel occlusions,1 selective white matter‐sparing infarction on post‐treatment MRI is associated with more favorable outcomes.2 Predicting ischemic core volume with perfusion imaging using the same CBF threshold for both gray and white matter may over‐estimate the ischemic core if CBF is between the gray and white matter thresholds.

Optimum duration of hyperventilation during electroencephalography

Hyperventilation (HV) is carried out for 3 minutes as a standard activation procedure in most routine electroencephalographic (EEG) procedures. The cerebral blood flow (CBF) reduction and the accompanying cerebral vasoconstriction caused by HV is believed to be the mechanism of EEG activation during HV. Some advocate for 5 minutes of HV, although the optimum duration is unknown. In this study, we measured the CBF continuously over the anterior temporal lobes using subdural probes, which use thermal diffusion flowmetry to measure CBF directly from the cerebral cortex. We sought to determine the duration of HV that produces the maximum reduction in CBF during routine HV in our epilepsy monitoring unit and prolonged the procedure for an additional 2 minutes for this study. Flowtronics® CBF probes were placed over the anterior temporal lobes in addition to the standard subdural strip placement for localization of their seizure focus in six patients who were candidates for epilepsy surgery. CBF was measured continuously for 2 minutes before and 5 minutes during HV for each patient. Time to reach maximum reduction of CBF for each attempt (11 temporal lobes) was computed. At 3 minutes, CBF reduction ranged from 11.6% to 40.0% from the pre-HV CBF level (mean 23.9%). At 5 minutes, CBF ranged from 14.3% to 42.0% (mean 25.7%). Six of the 11 measurements were steady or decreased slightly, and in the five other measurements, CBF showed a reverse trend after 3 minutes. A significant CBF reduction was attained in 3 minutes of HV in all trials. Continued HV after 3 minutes resulted in only a marginal (mean 1.8%) additional CBF reduction after 3 minutes. Thus, we propose that 3 minutes of HV is sufficient for EEG activation by the CBF criterion.

Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure

To study the effect of Unifuzol (L-arginine sodium succinate) on cognitive impairment, cerebral blood flow, and damage to the tissues of the hippocampus and cerebral cortex during a 10-day course of administration to rats with chronic cerebral ischemia (CCI) caused by bilateral stenosis of the common carotid arteries (CCA). The study was conducted on male rats with CCI caused by bilateral stenosis of the CCA by 60%. 40 days after surgery, rats received Unifusol (21, 42 and 84 ml/kg), nicergoline (10 mg/kg), citicoline (500 mg/kg) or placebo (0.9% NaCl) for 10 days. Next, cognitive impairments were assessed in the Morris Water Maze and the New Object Recognition (NOR) test, as well as the level of motor and exploratory activity in the Open Field test. The level of cerebral blood flow was determined immediately after the CCA stenosis and at the end of the experiment. Animals were euthanized in a CO2 incubator, after which the brain was removed and subjected to morphometric analysis. In animals that were modeled with CCA stenosis, pronounced behavioral and cognitive impairments occurred as a result of a decrease in blood flow in the vessels of the brain and subsequent changes in the tissues of the hippocampus and the cerebral cortex. Intravenous course administration of Unifuzol at doses of 42 and 84 ml/kg to animals with CCI was comparable in efficiency to nicergoline and citicoline, which was expressed in greater preservation of the cognitive abilities of animals in the Morris Water Maze and NOR tests. In the Open Field test, animals injected with Unifusol at doses of 42 and 84 ml/kg performed more acts of motor and exploratory activity than animals from the placebo group, and had a higher level of cerebral blood flow (compared to animals that were injected with citicoline). Based on the results of a morphological study, it was found that the most significant neuroprotective effect was provided by nicergoline and Unifuzol (at doses of 42 and 84 ml/kg). Unifuzol at a course of administration at doses of 42 and 84 ml/kg, comparable to the reference drugs nicergoline and citicoline, reduces the severity of psychoneurological deficit in animals with CCI, comparable to them improves the microcirculation of brain tissues, preventing damage to brain tissues.

Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes.

Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.

Relationship between consciousness level and perfusion computed tomography in patients with prolonged disorders of consciousness.

We assessed the relationship between consciousness level and values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) obtained by whole-brain perfusion computed tomography (pCT) in patients with prolonged disorders of consciousness (pDOC). This study included 29 patients in vegetative state (VS), 34 with minimally consciousness state minus (MCS-), and 13 with minimally consciousness state plus (MCS+). All patients were evaluated using the Coma Recovery Scale-Revised (CRS-R), the Glasgow Coma Scale (GCS), and the Full Outline of UnResponsiveness (FOUR). The values of CBF, CBV, MTT, and TTP were obtained from patients who underwent pCT. Differences in CBF, CBV, MTT, and TTP were compared between the three types of pDOC. Correlations between the CRS-R, GCS, and FOUR scores and the pCT results were analyzed. Among the three groups, patients in VS showed a significantly decreased CBF in the bilateral frontal lobe, thalamus, temporal lobe, occipital lobe, brainstem, and damaged part. CBV was significantly reduced in patients with VS in the bilateral frontal lobe, thalamus, temporal lobe, brainstem, and damaged part. The total CRS-R, GCS, and FOUR scores were positively correlated with CBF, CBV, and TTP in almost all regions of interest. Reductions in CBF and CBV calculated with pCT are associated with impaired consciousness and perfusion CT could be a promising tool in evaluating the conscious level in patients with pDOC.

Effect of Voxelotor on Cerebral Perfusion and Cerebral Oxygen Metabolism in Adult Patients with Sickle Cell Disease; Preliminary Results of the Coverage Study

Background: Sickle cell disease (SCD) is characterized by hemolytic anemia and a hyperdynamic circulation resulting in impaired cerebral hemodynamics and perfusion, culminating in ischemic damage of the brain. SCD is strongly associated with overt strokes or silent cerebral infarctions (SCI) which have been related to elevated flow in the median cerebral artery in children measured by transcranial Doppler. Patients with SCD have an increased cerebral blood flow (CBF) to maintain adequate oxygen delivery (OD). Previously, we and others have demonstrated with special MRI techniques that despite the maintained OD, cerebral metabolic rate of oxygen (CMRO2) is reduced in SCD due to reduced oxygen extraction fraction (OEF), which in turn is strongly related to CBF and hemoglobin (Hb) level. Voxelotor is a small molecule that reversibly binds to Hb and increases its oxygen affinity, thereby decreasing Hb polymerization and sickling. The resulting decreased hemolytic anemia can potentially ameliorate cerebral hemodynamics and perfusion, the increased oxygen affinity may reduce the offloading of oxygen. The aim of our study is to assess the effects of voxelotor on markers of cerebral perfusion and oxygen metabolism. In addition, the effect of voxelotor on the hyperdynamic cardiac function was assessed. Methods: This single-arm, interventional trial is being conducted in a tertiary hospital in Amsterdam, The Netherlands. Adult SCD patients with the severe genotypes of HbSS and HbSβ0-thalassemia were eligible for inclusion. Other major inclusion criteria were: Hb ≤ 10.5 g/dL and in case of hydroxyurea use, a stable dose for at least 90 days. Major exclusion criteria were: regular transfusions or a transfusion within 90 days prior to inclusion, hospitalization for vaso-occlusive crisis ≤ 14 days before inclusion. At baseline and after 3 months of voxelotor treatment (1500 mg pd), MRI scans, echocardiography and laboratory assessments were performed. Time-encoded arterial spin labeling was performed to obtain CBF measurements, gray matter CBF was derived by using white matter and gray matter masks. T2 relaxation under spin tagging was performed in order to calculate OEF. Oxygen delivery and CMRO2 were calculated: formula, CBF x OD, with the OD calculated from OEF and oxygen content. Maximal tricuspid regurgitation velocity (TRVmax) was assessed by trans-thoracic echocardiography as a marker of hyperdynamic circulation. N-Terminal pro-B-type natriuretic peptide (NT-proBNP) was measured as a marker of cardiac stress/dilatation. Parametric data are presented with mean and SD and analyzed by a paired T-test and non-parametric data with median and IQR, and analyzed by a Wilcoxon signed-rank test. Results: Preliminary results of 15 patients (HbSS/HbSβ0-thalassemia, 11/4, mean age 38 years (SD 10), 4 female) who completed their 3 month follow-up are presented here. Upon 3 months of voxelotor treatment, Hb levels significantly increased, 7.6 g/dL, (IQR 6.9 - 8.2) compared to 10.0 g/dL (IQR; p < 0.001), and hemolysis significantly reduced, represented by reticulocyte count, bilirubin and LDH levels (p = < 0.05; Table 1). After 3 months of treatment also a significant increase in oxygen delivery from 6.4 to 8.2 ml O2/100g/min (p = 0.006) was observed, which was primarily due to the increased Hb levels. However, CBF and CMRO2 did not change significantly after 3 months of voxelotor treatment (Table 2) while OEF decreased significantly at 3 months as compared to baseline (from 28.9% to 23.2%, p = 0.002) (Table 2). No significant changes in NT-proBNP levels and TRVmax were observed (Table 1) although a significant decrease was observed in patients with NT-proBNP-levels >160 at baseline (213 (IQR 161 - 254) ng/L vs 152 (IQR 50 -163) ng/L; p = 0.028)). Conclusion: In this preliminary study, no changes in cerebral hemodynamics (CBF) and oxygen metabolic rate (CMRO2) were observed, despite an increased cerebral oxygen delivery due to improvement of Hb levels. CMRO2 remained unchanged as a result of diminished OEF, based on the calibration according to the Li-Bush model, most likely due to the increased oxygen affinity attributed to voxelotor. With respect to the cardiac measures of the circulatory state, no effect on NT-proBNP levels and TRVmax was observed although a significant decrease in NT-proBNP-levels was observed in a post-hoc analysis of patients with elevated NTproBNP levels at baseline. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 318: Improvement In Cerebral Blood Flow Assessed By A Laser Speckle Imaging After Extracorporeal Cardiopulmonary Resuscitation In Rats

Introduction: The effect of extracorporeal cardiopulmonary resuscitation (ECPR) on recovery of cerebral blood flow (CBF) after achieving a return of spontaneous circulation (ROSC) has been undetermined. The objective of this study was to determine the impact of ECPR on the changes of CBF post-ROSC in a rat model of prolonged cardiac arrest (CA) and ECPR. Methods and Results: Adult Sprague-Dawley male rats (400- 500g) were subjected to 20-min of asphyxia CA whereupon animals were mechanically ventilated and resuscitated by conventional manual chest compression (CCPR, n = 6) or ECPR using venous-arterial cardiopulmonary bypass (ECPR, n = 5). Epinephrine was (20 μg/kg) intravenously injected once during CCPR but not ECPR. In the ECPR group, cardiopulmonary bypass was weaned 30 min after ROSC. ROSC was defined as achieving a mean arterial pressure &gt; 60 mmHg. Serial changes in CBF were measured at baseline and 2 h after ROSC using the laser speckle imaging system. There was no difference in time to CA and time to ROSC as well as hemodynamics for 2 h after ROSC between the two groups. Representative CBF images at 0, 10, 60, and 120 min after ROSC are shown in Fig. 1A. As expected, CCPR resulted in a hyperemic phase at 10 min and then a hypoperfusion phase (~ 50 % of CBF reduction from baseline) at 60 min or later after ROSC. In the ECPR group, CBF maintained at baseline level even at 60 and 120 min after ROSC. Further, CBF levels at 60 and 120 min after ROSC were markedly higher in the ECPR group than in the CCPR group ( Fig. 1B ). Conclusions: Our data using laser speckle imaging suggests that ECPR is likely to improve CBF shortly after ROSC compared to CCPR.

Cerebral blood flow alterations in migraine patients with and without aura: An arterial spin labeling study

BackgroundMigraine aura is a transient, fully reversible visual, sensory, or other central nervous system symptom that classically precedes migraine headache. This study aimed to investigate cerebral blood flow (CBF) alterations of migraine with aura patients (MwA) and without aura patients (MwoA) during inter-ictal periods, using arterial spin labeling (ASL).MethodsWe evaluated 88 migraine patients (32 MwA) and 44 healthy control subjects (HC) who underwent a three-dimensional pseudo-continuous ASL MRI scanning. Voxel-based comparison of normalized CBF was conducted between MwA and MwoA. The relationship between CBF variation and clinical scale assessment was further analyzed. The mean CBF values in brain regions showed significant differences were calculated and considered as imaging features. Based on these features, different machine learning–based models were established to differentiate MwA and MwoA under five-fold cross validation. The predictive ability of the optimal model was further tested in an independent sample of 30 migraine patients (10 MwA).ResultsIn comparison to MwoA and HC, MwA exhibited higher CBF levels in the bilateral superior frontal gyrus, bilateral postcentral gyrus and cerebellum, and lower CBF levels in the bilateral middle frontal gyrus, thalamus and medioventral occipital cortex (all p values < 0.05). These variations were also significantly correlated with multiple clinical rating scales about headache severity, quality of life and emotion. On basis of these CBF features, the accuracies and areas under curve of the final model in the training and testing samples were 84.3% and 0.872, 83.3% and 0.860 in discriminating patients with and without aura, respectively.ConclusionIn this study, CBF abnormalities of MwA were identified in multiple brain regions, which might help better understand migraine-stroke connection mechanisms and may guide patient-specific decision-making.