Significant Decrease In Cerebral Blood Flow Research Articles

Oxygen extraction fraction change in M1-M6 brain regions of patients with unilateral or bilateral middle cerebral artery occlusion.

Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) can be measured using arterial spin labeling (ASL) and quantitative susceptibility mapping (QSM) sequences, respectively. ASL and QSM sequences were performed on 13 healthy participants and 46 patients with unilateral or bilateral Middle cerebral artery (MCA) occlusion. M1-M3 and M4-M6 correspond to anterior, lateral, and posterior MCA territories within the insular ribbon and centrum semiovale, respectively. In patients with unilateral MCA occlusion, significant decreases in CBF were observed in the lesions in M1, M3, M5 and M6 regions, as well as in the contralateral M3 and M5 regions. The OEF of the lesion in the M1-M4 and M6 regions, and the contralateral M1-M3 regions were significantly higher. Additionally, the cerebral metabolic rate of oxygen (CMRO2) in the lesions of the M3 and M6 regions, and the contralateral M3 region, were significantly lower compared to the corresponding regions of healthy participants. For patients with bilateral MCA occlusion, the CMRO2 in the left M5 region and the right M3 and M6 regions were significantly lower than that in the corresponding regions of healthy participants. In conclusion, abnormal hemodynamics occur in the contralateral hemisphere of patients with unilateral MCA occlusion.

Evaluation of the correlation between cerebral hemodynamics and blood pressure by comparative analysis of variation in cerebral blood flow in hypertensive versus normotensive individuals: A systematic review and meta-analysis.

Current understanding of the cerebral vascular response to variations in blood pressure (BP) among individuals with hypertension is limited. The aim of this meta-analysis was to determine the correlation between hypertension, risk of stroke, and cerebral blood flow (CBF). We reviewed studies published between 2000 and 2023 from PubMed, Google Scholar, and Science Direct that compared mean CBF in normotensive (NTN) and hypertensive (HTN) patients. A random effects model was used to construct the risk ratio (RR), 95% confidence interval (CI), forest plot, and inverse variance weighting. Additionally, a mixed-effects meta-regression was employed to examine the impact of study-specific patient variables. This meta-analysis included eight prospective cross-sectional studies published from 2002 to 2023. It revealed a significant average difference in the standard mean CBF of -0.45 (95% CI -0.60 to -0.30, I2 = 69%, P < 0.00001), distinguishing NTN from HTN subjects. A RR of 0.90 (95% CI 0.63 to 1.30, I2 = 89%, P = 0.04) indicated a significant decrease in CBF among individuals with hypertension. We found a statistically significant relationship between changes in diastolic and systolic BPs and the mean CBF (R -0.81, P = 0.001 and R = -0.90, P = 0.005, respectively). Our research demonstrates a strong relationship between elevated BP and reduced CBF, with hypertension reducing CBF compared to NTN individuals, by increasing cerebrovascular resistance.

Temporal Alterations in Cerebrovascular Glycocalyx and Cerebral Blood Flow after Exposure to a High-Intensity Blast in Rats.

The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.9 PSI/131 kPa peak pressure, 10.95 ms duration, and 70.26 PSI·ms/484.42 kPa·ms impulse) BOP exposure in rats. A significant reduction in the density of the glycocalyx was observed 2-3 h, 1-, and 3 days after the blast exposure. The glycocalyx recovered by 28 days after exposure and was associated with an increase in HS (14 and 28 days) and in HSPG/syndecan-2 and CS (28 days) in the frontal cortex. In separate experiments, we observed significant decreases in CBF and a diminished response to hypercapnia at all time points with some recovery at 3 days. Given the role of the glycocalyx in regulating physiological function of the cerebral vasculature, damage to the glycocalyx after BOP exposure may result in the onset of pathogenesis and progression of cerebrovascular dysfunction leading to neuropathology.

Diagnostic Value of Multi‐delay Multi‐parametric 3D pCASL in Early Alzheimer' Disease

AbstractBackgroundSingle post‐labeling delay (PLD) pseudo‐continuous arterial spin‐labeling (pCASL) measures cerebral blood Flow (CBF). The altered CBF is associated with cognitive decline in early Alzheimer’s disease (AD). However, multi‐delay pCASL that measures multi‐parametric measurements including CBF, arterial cerebral blood volume (aCBV) and arterial transit time (ATT) has rarely been applied to AD studies and its diagnostic performance to recognize AD in early stage remains unclear. The purpose of this study is to compare the diagnostic value between the CBF measured by single PLD pCASL and the CBF/aCBV/ATT measured by multi‐PLD pCASL for early‐stage AD.MethodBoth 1 PLD and 7 PLD 3D pCASL protocols on 3T GE scanner were performed within one MR session for 26 cognitively normal (CN), 37 mild cognitive impairment (MCI) and 39 AD subjects who were recruited in Chinese Imaging, Biomarkers, and Lifestyle Study of Ageing Project (CIBL) from April to October 2021. Comparisons on CBF/aCBV/ATT in 10 regions of interest (ROIs), including left and right regions of olfactory, post cingulate, hippocampus, cuneus and precuneus, were performed across different groups. The area under the curve (AUC) were assessed through receiver operating characteristic (ROC) analysis.ResultAll ROIs showed significant decrease in CBF and increase in ATT of AD groups compared with that of CN and MCI groups (P &lt; 0.05). There was no significant difference in aCBV between groups and CBF/ATT between CN and MCI (P &gt; 0.05). The area under the ROC curve (AUC) of CBF in ROIs for both3D pCASL protocols was similar for discriminating AD against HC (0.949 vs. 0.965 for 1 PLD vs. 7 PLD, respectively), AD against MCI (0.836 vs. 0.830), MCI against HC (0.686 vs. 0.786). However, the combination of CBF/aCBV/ATT in ROIs measured by 7 PLD 3D pCASL could significantly improve diagnostic performance, which AUC was 1.000, 0.967 and 0.918 for identifying AD against HC, AD against MCI and MCI against HC respectively.ConclusionMulti‐parametric perfusion data from multi‐delay pCASL can improve the diagnostic value of AD in early stage, which could be a promising imaging biomarker in AD patients.

Modelling spatiotemporal dynamics of cerebral blood flow using multiple-timepoint arterial spin labelling MRI.

Introduction: Cerebral blood flow (CBF) is an important physiological parameter that can be quantified non-invasively using arterial spin labelling (ASL) imaging. Although most ASL studies are based on single-timepoint strategies, multi-timepoint approaches (multiple-PLD) in combination with appropriate model fitting strategies may be beneficial not only to improve CBF quantification but also to retrieve other physiological information of interest. Methods: In this work, we tested several kinetic models for the fitting of multiple-PLD pCASL data in a group of 10 healthy subjects. In particular, we extended the standard kinetic model by incorporating dispersion effects and the macrovascular contribution and assessed their individual and combined effect on CBF quantification. These assessments were performed using two pseudo-continuous ASL (pCASL) datasets acquired in the same subjects but during two conditions mimicking different CBF dynamics: normocapnia and hypercapnia (achieved through a CO2 stimulus). Results: All kinetic models quantified and highlighted the different CBF spatiotemporal dynamics between the two conditions. Hypercapnia led to an increase in CBF whilst decreasing arterial transit time (ATT) and arterial blood volume (aBV). When comparing the different kinetic models, the incorporation of dispersion effects yielded a significant decrease in CBF (∼10-22%) and ATT (∼17-26%), whilst aBV (∼44-74%) increased, and this was observed in both conditions. The extended model that includes dispersion effects and the macrovascular component has been shown to provide the best fit to both datasets. Conclusion: Our results support the use of extended models that include the macrovascular component and dispersion effects when modelling multiple-PLD pCASL data.

Evaluating the pharmacodynamic effects of padsevonil in healthy volunteers using simultaneous [11C]-UCB-J PET and MR Arterial Spin Labeling measurements

IntroductionIntegrated PET-MR scanners can measure simultaneously tracer binding, downstream cerebral blood flow (CBF) and neuronal activation. An integrated GE Signa PET-MR system was used to combine [11C]-UCB-J PET scanning with MR Arterial Spin Labeling (ASL) measurements to evaluate the effects of padsevonil (PSL) on SV2A occupancy and CBF simultaneously. MethodsPET-MR scanning was performed in 10 healthy controls (8M/2F; 27.6 ​± ​10.0 ​yrs) at baseline, and at two timepoints (post1: 2−24h and post2: 6−30h) after administration of a single PSL dose (6.2−100 ​mg). Dynamic [11C]-UCB-J PET scanning with arterial blood sampling was performed to estimate distribution volumes and corresponding SV2A occupancies. Simultaneously, MR ASL data were acquired and spatially normalized to Montreal Neurological Institute (MNI) space for voxel wise analysis while brain Volume-Of-Interest (VOI) were defined using a simplified Hammers atlas. ResultsPET measurements showed a SV2A occupancy range of 57–98% and 16−63% and a corresponding PSL plasma concentration range of 3.6–189.23 ​ng/mL and 1.3–9.8 ​ng/mL for post1 and post2, respectively. When comparing post1 to baseline ASL measurements, a VOI-based analysis detected a significant CBF decrease in thalamus, insula, cerebellum, posterior cingulate cortex, and brain stem, which was confirmed by a voxel-wise analysis comparing baseline and post1 ASL measurements and identifying significantly different clusters covering the same brain regions. In addition, we demonstrated CBF recovery in these brain regions for the post2 ASL measurements compared to baseline measurements. For the thalamus, a VOI-based correlation analysis detected a significant correlation between PSL plasma concentration and CBF decrease relative to baseline conditions. DiscussionA pattern of local and dose dependent CBF decrease was demonstrated following PSL administration. More generally, these findings present the potential of simultaneous PET and ASL measurements to follow the time course of drug effects and to differentiate between the efficacy of different drugs in patient groups.

Dynamic cerebral blood flow changes with FOXOs stimulation are involved in neuronal damage associated with high-altitude cerebral edema in mice

Acute hypobaric hypoxia (AHH) exposure causes altitude mountain sickness (AMS) and life-threatening high altitude cerebral edema (HACE). Despite decades of research, the role of cerebral blood flow (CBF) changes in the pathophysiology of severe AMS remains unclear. The current study evaluated spatiotemporal responses of CBF associated with HACE in mice during the early stages of ascent to high altitudes. First, mice were exposed to AHH to test their tolerance to increasing altitudes (3000–8000 m). Because of its significant influence on both locomotor activity and rotarod behavior tests in mice, further observations were initiated at an altitude of 6000 m to investigate the specific pathophysiology of AMS. Compared with controls, laser speckle contrast imaging (LSCI) revealed a significant decrease in CBF during the early stage (0.5–24 h) at an altitude of 6000 m that was accompanied by a significant increase in brain water content (BWC). Moreover, observations of brain lipid oxidative damage and oxidative stress during the early stage of AHH exposure revealed DNA and cellular damage in cortical and hippocampal regions. Transcriptome profiling of the hippocampus revealed upregulation of forkhead box transcription factors. Similarly, western blot assays revealed upregulation of FOXO1a, FOXO3a, caspase-3 and Bax, and downregulation of Bcl-2, indicating a temporal influence of AHH on mitochondrial function and neuronal apoptosis. Thus, we found that the pathophysiology of HACE occurred with dynamic CBF changes, which triggered oxidative stress and neuronal damage in the mouse brain after AHH exposure. Our findings provide potential strategies for treatment of AHH in the future.

Cerebral blood flow and oxygenation in rat brain after soman exposure

Nerve agent exposure can cause debilitating neurological damage even with treatment. Currently accepted treatments involve attenuating the cholinergic crisis and seizure onset but do not focus directly on neuroprotection. Hence, there is a need for improved treatments to reduce neurological deficits. It is important to understand the pathophysiology of nerve agent mediated injury in order to identify effective treatment targets. Nerve agent-induced seizures are believed to be the main contributor to the neuropathology. Recently seizures have been shown to cause vascular changes that may actually attenuate neurological damage. This study evaluated the effect of soman-induced convulsive seizures on the relationship between CNS oxygen consumption and supply.To simultaneously assess changes in oxygenation and perfusion, rats were implanted with permanently fixed fiber-optic tissue oxygen sensing probes in the motor cortex and imaged with continuous arterial spin labelling MRI to measure cerebral blood flow. Baseline tissue oxygen tension (ptO2) and cerebral blood flow (CBF) were measured in isoflurane anaesthetized rats at least one day prior to soman or saline exposure. Rats were pretreated with HI-6 dimethansulfonate and atropine methyl nitrate (125 mg/kg and 20 mg/kg; intraperitoneal) followed by a convulsive dose of soman (90 μg/kg; subcutaneous) or equal volume of saline. Three additional treatments of HI-6/AMN were administered to improve survival. At 1.5 -hs after exposure, ptO2 and cerebral blood flow measurements were conducted.There was a significant decrease in CBF 1.5 -hs following soman exposure but no change in ptO2 was found. When we correlated ptO2 and CBF, for a given ptO2, there was lower CBF following soman exposure. This may indicate metabolism is inhibited, possibly because of mitochondrial impairment, therefore reducing oxygen demand. These data show hypoperfusion in brain following soman exposure which would be expected to contribute to soman-related neuropathology.

Computed tomography perfusion imaging after aneurysmal subarachnoid hemorrhage can detect cerebral vasospasm and predict delayed cerebral ischemia after endovascular treatment.

Background: Endovascular treatment (ET) can improve angiographic cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage, but was unrelated to clinical outcomes in previous analyses. Appropriate detection of CV and precise indications for ET are required. This study investigated whether changes in computed tomography perfusion (CTP) parameter can determine indications for ET in CV and predict its effectiveness.Methods: Participants comprised 140 patients who underwent neck clipping or coil embolization. CTP was performed a week after aneurysmal treatment or when clinical deterioration had occurred. Patients were divided into ET and non-ET groups by propensity score matching. In addition, the ET group was divided into subgroups with and without new cerebral infarction (CI). All CTP images in the three groups were retrospectively investigated qualitatively and quantitatively. CI was diagnosed from CT at 3 months postoperatively.Results: Of the 121 patients examined, 15 patients (11%) needed ET. In qualitative analysis, all ET group patients displayed extension of time-to-peak (TTP) at the region of vasospastic change, regardless of the presence of CI. Quantitative analysis showed significant decreases in cerebral blood volume (P < 0.01), cerebral blood flow (CBF) (P < 0.001), and extension in TTP (P < 0.01) in the ET group compared with the non-ET group. A significant decrease in CBF (P < 0.001) and extension in mean transit time (P < 0.001) was seen in the ET with CI subgroup compared with the ET without CI subgroup.Conclusion: CTP in the vasospastic period may be an indication for ET and predict the effectiveness of ET for CV to improve clinical outcomes.

Cerebral glucose metabolism and Cerebral blood flow in thyroid dysfunction: An Activation Likelihood Estimation Meta-analysis

Thyroid dysfunction is frequently associated with functional disturbances of the brain. We performed a meta-analysis of previous positron emission tomography and single-photon emission computed tomography studies using a coordinate-based technique of activation-likelihood estimation (ALE) to investigate the potential background of neuropsychiatric complications in patients with hypo- and hyperthyroidism. We performed a systematic search of MEDLINE and EMBASE for English-language publications using the keywords of “positron emission tomography”, “single-photon emission computed tomography”, and “thyroid”. The software GingerALE ver 2.3.6 was used to transform all reported coordinates into stereotactic Montreal Neurological Institute space. A threshold of uncorrected p < 0.001 (minimum volume of 200 mm3) was applied to the resulting ALE map using cerebral metabolic rate of glucose (CMRglu), and cerebral blood flow (CBF). Six studies were eligible for inclusion in the study; 4 studies of cerebral metabolic rate of CMRglu, and 2 studies of CBF. In hypothyroidism, significant decreases in CMRglu were identified in 3 clusters including left anterior cingulate, right inferior occipital gyrus, and right cuneus. In hyperthyroidism, a significant decrease in CMRglu was identified in right superior frontal gyrus. In hypothyroidism, a significant decrease in CBF was observed in left postcentral gyrus. In conclusion, several brain regions showed altered CMRglu and CBF in patients with thyroid dysfunction compared with euthyroid controls. These findings might account for underlying mechanisms of thyroid hormones on psychological and physiological effects on brain.

Subarachnoid Hemorrhage Pattern Predicts Acute Cerebral Blood Flow Response in theRat.

There is considerable variability in the presentation of patients with acute subarachnoid hemorrhage (aSAH). Evidence suggests that a thick, diffuse clot better predicts the development of delayed cerebral ischemia and poor outcomes. In a rodent model of acute SAH, we directly measured the effects of the volume of blood injected versus the pattern of distribution of hemorrhage in the subarachnoid space on markers of early brain injury, namely, cerebral blood flow (CBF), cerebrospinal fluid (CSF) concentrations of P450 eicosanoids and catecholamines, and cortical spreading depolarizations (CSDs). There is a significant decrease in CBF, an increase in CSF biomarkers, and a trend toward increasing frequency and severity of CSDs when grouped by severity of hemorrhage but not by volume of blood injected. In severe hemorrhage grade animals, there was a progressive decrease in CBF after successive CSD events. These results suggest that the pattern of SAH (thick diffuse clots) correlates with the "clinical" severity of SAH.

Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of 15O-gas in mice with bilateral common carotid artery stenosis

Positron emission tomography with 15O-labeled gases (15O-PET) is important for in vivo measurement of cerebral oxygen metabolism both in clinical and basic settings. However, there are currently no reports concerning 15O-PET in mice. Here, we developed an 15O-PET method applicable to mice with spontaneous respiration of 15O-gas without a tracheotomy catheter. Sequential 15O-PET was also performed in a mouse model of chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) induced by placement of microcoils. 15O-gas with isoflurane was supplied to the nose of mouse with evacuation of excess 15O-gas surrounding the body. 15O-PET was performed on days 3, 7, 14, 21, and 28 after surgery. Cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were calculated in whole brains. A significant decrease in CBF and compensatory increase in OEF in the BCAS group produced CMRO2 values comparable to that of the sham group at three days post-operation. Although CBF and OEF in the BCAS group gradually recovered over the first 28 days, the CMRO2 showed a gradual decrease to 68% of sham values at 28 days post-operation. In conclusion, we successfully developed a noninvasive 15O-PET method for mice.

Cerebral Blood Flow Alterations in Acute Sport-Related Concussion.

Sport-related concussion (SRC) is a major health problem, affecting millions of athletes each year. While the clinical effects of SRC (e.g., symptoms and functional impairments) typically resolve within several days, increasing evidence suggests persistent neurophysiological abnormalities beyond the point of clinical recovery after injury. This study aimed to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared CBF maps assessed in 18 concussed football players (age, 17.8 ± 1.5 years) obtained within 24 h and at 8 days after injury with a control group of 19 matched non-concussed football players. While the control group did not show any changes in CBF between the two time-points, concussed athletes demonstrated a significant decrease in CBF at 8 days relative to within 24 h. Scores on the clinical symptom (Sport Concussion Assessment Tool 3, SCAT3) and cognitive measures (Standardized Assessment of Concussion [SAC]) demonstrated significant impairment (vs. pre-season baseline levels) at 24 h (SCAT, p < 0.0001; SAC, p < 0.01) but returned to baseline levels at 8 days. Two additional computerized neurocognitive tests, the Automated Neuropsychological Assessment Metrics and Immediate Post-Concussion and Cognitive Testing, showed a similar pattern of changes. These data support the hypothesis that physiological changes persist beyond the point of clinical recovery after SRC. Our results also indicate that advanced ASL MRI methods might be useful for detecting and tracking the longitudinal course of underlying neurophysiological recovery from concussion.

Stability of MR brain-perfusion measurement using arterial spin labeling.

Arterial spin labeling (ASL) is an MR technique for assessment of cerebral blood flow (CBF) that does not require use of contrast agents which makes it a less invasive alternative to the 15O-H2O-PET measurement. The repeatability of ASL has been studied extensively but mainly in young healthy volunteers. We have tested repeatability of ASL under realistic clinical conditions in elderly brain tumor patients acquired with a Philips Ingenuity TF PET/MR in the context of an ongoing 11C-Methionine PET/MR study. Twenty three patients (age 54.8±13.0 y) were scanned on two or more session. The patients underwent 6 weeks of concurrent radiochemotherapy with Temozolomide between the first session and second measurement. The mean relative difference of gray matter CBF was 18.6% between the first two session and 13.0% for the second session and further on. The mean gray matter CBF was 46.6±7.2 mL/min/100 g on the first sessions and there was a significant decrease of 9.8% between first and second session (p=0.027). In summary, the ASL presents measurement of CBF with reasonable repeatability also in elderly patients under clinical conditions when it is not possible to control for all sources of variation. Significant decrease of CBF in healthy tissue was observed after the radiochemotherapy. Prospectively, the ASL data together with the also acquired 11C-Methionine PET will be evaluated regarding their separate and combined ability to predict patient outcome and effectiveness of the performed radiochemotherapy.

Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.

Abstract 064: Toll-like Receptor 2 Signaling Contributes To Cerebrovascular Dysfunction And Decreased Cerebral Blood Flow In Type-1 And Type-2 Diabetes.

We have shown that type 2 diabetic Goto-Kakizaki (GK) rats develop cerebrovascular endothelial dysfunction, impaired cerebral blood flow (CBF) and mild cognitive deficits. It is increasingly recognized that vascular cognitive impairment may be a new complication of the disease in both type 1 and type 2 diabetes. Toll-like receptor-2 (TLR2) plays a role in cardiovascular complications of diabetes but its involvement in diabetic cerebrovascular disease is unknown. Since brain function heavily depends on constant perfusion, and decreased CBF precedes development of inflammation and cognitive deficits, we hypothesized that enhanced TLR2 signaling in both type 1 and 2 diabetes would contribute to cerebrovascular dysfunction and decreased CBF. Endothelium-dependent relaxation was assessed by measuring acetylcholine (ACh, 10-9 -10-4 M) induced dilatory response in basilar arteries from GK rats in the presence and absence of an anti-TLR2 (1μg) antibody. Vascular contractility to serotonin (10-9 -10-5 M) stimulation was also assessed. Area under the curve (AUC) and maximal effective concentration (Emax as % of max KCl response) were calculated as indices of total relaxation and total contraction, respectively. Basilar artery relaxation was significantly improved in the vessels preincubated (30’) with antiTLR2 (184.8± 24.0 vs. 87.7± 4, p =0.007). The EMax in response to serotonin stimulation in the anti-TLR2 treated vessels was not significantly different than the vessels from the untreated diabetic GK rats (110.6± 4.9% vs 99.4.±4.5%). To further assess the in vivo functional effects of TLR2 signaling, CBF (relative intensity) was measured using laser speckle imaging in wild type and TLR2-knockout (KO) mice using an STZ induced diabetes model. Six weeks after induction of diabetes, wild-type diabetic mice exhibited a significant decrease in CBF vs. control (210±22.5 vs. 300.3±18.4, p&lt;0.05). This decrease in cerebral perfusion was attenuated in the TLR2-KO diabetic mice compared to TLR2 KO control (322.6±10.1 vs. 344. 5±11. 04). These findings suggest that TLR2 signaling leads to vascular dysfunction through decreased endothelium dependent relaxation, and could contribute to decreased CBF in diabetes predisposing to vascular cognitive impairment.

Pre- and Post-Angioplasty Perfusion CT with Acetazolamide Challenge in Patients with Unilateral Cerebrovascular Stenotic Disease

ObjectivePerfusion computed tomography (PCT) has the ability to measure quantitative value and produce maps of mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV). We assessed cerebral hemodynamics by using these parameters and acetazolamide (ACZ) challenge for pre- and post-procedural evaluation in patients with unilateral cerebrovascular stenotic disease.MethodsThirty patients underwent pre-procedural PCT with ACZ challenge, and 24 patients (80%) was conducted follow up PCT after angioplasty with same protocol. The mean MTT, CBF, and CBV were measured and compared in both middle cerebral arterial (MCA) territories before and after ACZ challenge. Hemispheric ratio and percent change after ACZ challenge were calculated before and after angioplasty.ResultsThe mean stenosis rate was 76.6%. Significant increases in MTT (32.6%, p=0.000) and significant decreases in CBF (-14.2%, p=0.000) were found in stenotic side MCA territories. After ACZ challenge, there were significant changes in MTT (37.4%, p=0.000), CBF (-13.1%, p=0.000), and CBV (-10.5%, p=0.001) in pre-procedural perfusion study. However, no significant increases were found in MTT, or decreases in CBF and CBV in post-procedural study. There were no significant changes after ACZ challenge also. In addition, the degrees of these changes (before and after ACZ challenge) were highly correlated with the stenotic degrees in pre-procedural perfusion study.ConclusionPCT with ACZ challenge appears to be a useful tool to assess the cerebral perfusion status especially in patients with unilateral symptomatic stenotic disease.

Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: A perfusion fMRI study

This article investigates the effects of postherpetic neuralgia (PHN) on resting-state brain activity utilizing arterial spin labeling (ASL) techniques. Features of static and dynamic cerebral blood flow (CBF) were analyzed to reflect the specific brain response to PHN pain. Eleven consecutive patients suffering from PHN and 11 age- and gender-matched control subjects underwent perfusion functional magnetic resonance imaging brain scanning during the resting state. Group comparison was conducted to detect the regions with significant changes of CBF in PHN patients. Then we chose those regions that were highly correlated with the self-reported pain intensity as “seeds” to calculate the functional connectivity of both groups. Absolute CBF values of these regions were also compared across PHN patients and control subjects. Significant increases in CBF of the patient group were observed in left striatum, right thalamus, left primary somatosensory cortex (S1), left insula, left amygdala, left primary somatomotor cortex, and left inferior parietal lobule. Significant decreases in CBF were mainly located in the frontal cortex. Regional CBF in the left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and further comparison showed that the regional CBF in these regions is significantly higher in PHN groups. Functional connectivity results demonstrated that the reward circuitry involved in striatum, prefrontal cortex, amygdala, and parahippocampal gyrus and the circuitry among striatum, thalamus, and insula were highly correlated with each element in PHN patients. In addition, noninvasive brain perfusion imaging at rest may provide novel insights into the central mechanisms underlying PHN pain.

Recovery of Normal Hemodynamic Activities after Long-term Medication in a Patient with Left Internal Carotid Arterial Occlusion

Aspirin, clopidogrel, cilostazol, and statins are thought to reduce the risk of cerebral infarction in patients with intracranial arterial stenosis. We present a case of multiple intracranial arterial stenoses in which increased cerebral blood flow (CBF) was demonstrated after long-term medical therapy. A 68-year-old man with a history of cerebral infarction showed complete occlusion of the left internal carotid artery with severe stenoses in the A1 segment of the left anterior cerebral artery (ACA) and the left posterior communicating artery resulting in poor visualization of the left middle cerebral artery (MCA) on magnetic resonance angiography (MRA). Administration of aspirin and clopidogrel prevented ischemia from recurring for 1 year; however, the stenoses never improved. Technetium-99m-L, L-ethylcysteinate dimer single-photon emission computed tomography (SPECT) demonstrated a significant decrease in CBF in the territory of the left MCA. Anastomosis between the superficial temporal artery and the MCA was recommended to the patient because no supplementary blood supply was expected through either the left A1 or posterior communicating artery. However, the patient refused surgery because of the associated risks. To enhance vasodilation, clopidogrel was replaced by cilostazol. One year later, the stenoses had partially improved. Further treatment with aspirin, cilostazol, simvastatin, and nateglinide contributed to the significant increase in CBF with normal hemodynamics, as shown with acetazolamide-loading SPECT. The goal of treatment for intracranial arterial stenosis is to supply sufficient blood flow to the brain rather than to completely dilate the stenotic artery. Long-term treatment with aspirin, cilostazol, simvastatin, and nateglinide might help increase CBF in some patients with intracranial arterial stenosis.

Mapping of Cerebral Oxygen Extraction Fraction Changes with Susceptibility-weighted Phase Imaging

To develop a map to detect changes in oxygen extraction fraction (OEF) utilizing susceptibility-weighted (SW) phase images and to correlate such changes in OEF with those in cerebral blood flow (CBF). The study protocol was approved by the institutional review board, and written informed consent was obtained from all subjects. Eight healthy volunteers (mean age ± standard deviation, 29.8 years ± 4.6) were included in the study. Subjects were evaluated by using SW imaging, and the change in OEF was calculated by subtracting the image at baseline from one of the images obtained during six different conditions, including two at resting state, three different types of respiratory challenges, and one drug challenge with acetazolamide. Arterial spin labeling was carried out to measure CBF, while SW imaging was used to generate maps of change in OEF in response to a given condition. Statistical tests included one-way analysis of variance and Dunnett multiple comparisons to compare among the six conditions the magnitude of change from baseline for both OEF and CBF, by using the OEF change at resting state (resting 1) as the control. Hyperventilation caused a statistically significant decrease in CBF (-29.3%, P < .001) and an increase in OEF (+5.2%, P < .001) compared with the control, resting 1 (+2.2%, -0.7%, respectively). Acetazolamide caused a significant increase in CBF (+39.7%, P < .001) and a decrease in OEF (-3.4%, P = .040). Carbogen also induced a CBF increase (+16.2%); however, the change was not significant (P = .090), even though OEF decreased significantly (-4.2%, P = .003). Oxygen administration resulted in a significant CBF decrease (-27.2%, P < .001), whereas OEF showed no significant difference (-0.6%, P > .99). Maps of changes in OEF generated from SW phase images revealed changes in OEF corresponding to anticipated changes in CBF induced by various conditions; SW phase imaging might, in the future, be applied to evaluate cerebrovascular and other cerebral disorders in which changes in oxygen metabolism are important for planning therapeutic strategies.