Global Cortical Cerebral Blood Flow Research Articles

Higher intracranial pressure variability is associated with lower cerebrovascular resistance in aneurysmal subarachnoid hemorrhage

Higher intracranial pressure variability (ICPV) has been associated with a more favorable cerebral energy metabolism, lower rate of delayed ischemic neurologic deficits, and more favorable outcome in aneurysmal subarachnoid hemorrhage (aSAH). We have hypothesized that higher ICPV partly reflects more compliant and active cerebral vessels. In this study, the aim was to further test this by investigating if higher ICPV was associated with lower cerebrovascular resistance (CVR) and higher cerebral blood flow (CBF) after aSAH. In this observational study, 147 aSAH patients were included, all of whom had been treated in the Neurointensive Care (NIC) Unit, Uppsala, Sweden, 2012–2020. They were required to have had ICP monitoring and at least one xenon-enhanced computed tomography (Xe-CT) scan to study cortical CBF within the first 2 weeks post-ictus. CVR was defined as the cerebral perfusion pressure in association with the Xe-CT scan divided by the concurrent CBF. ICPV was defined over three intervals: subminute (ICPV-1m), 30-min (ICPV-30m), and 4 h (ICPV-4h). The first 14 days were divided into early (days 1–3) and vasospasm phase (days 4–14). In the vasospasm phase, but not in the early phase, higher ICPV-4h (β = − 0.19, p < 0.05) was independently associated with a lower CVR in a multiple linear regression analysis and with a higher global cortical CBF (r = 0.19, p < 0.05) in a univariate analysis. ICPV-1m and ICPV-30m were not associated with CVR or CBF in any phase. This study corroborates the hypothesis that higher ICPV, at least in the 4-h interval, is favorable and may reflect more compliant and possibly more active cerebral vessels.

CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage.

Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI. CBF was assessed by bedside xenon-enhanced CT at days 0-3, 4-7, and 8-12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group. In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1-33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2-46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9-48.5) at baseline and 31.6 (IQR 22.4-35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients. Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT

BackgroundCompromised cerebral blood flow (CBF) is a crucial factor in delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Repeated measurement of CBF may improve our understanding of the temporal dynamics following SAH. The aim of this study was to assess CBF at different phases of the acute course in poor-grade SAH patients, hypothesizing more pronounced disturbances at day 4–7, and that the initial level of CBF determines the following course of CBF.MethodsMechanically ventilated SAH patients were scheduled for bedside measurement of regional and global cortical CBF at day 0–3, 4–7, and 8–12, using xenon-enhanced computed tomography in a mobile setup. Patients were dichotomized depending on high or low initial global cortical CBF and cutoff level 30 ml/100 g/min.ResultsEighty-one patients were included, and 51 had measurements at day 0–3 and 4–7. In patients with high initial CBF, the level was unchanged at day 4–7; 37.7 (IQR 32.6–46.7) ml/100 g/min versus 36.8 (IQR 29.5–44.8). The low-CBF group showed a slight increase from 23.6 (IQR 21.0–28.1) ml/100 g/min to 28.4 (IQR 22.7–38.3) (P = 0.025), still markedly lower than the high-CBF group (P = 0.016). In the low-CBF group, CBF increased in patients who received hypertension, hypervolemia, and hemodilution (HHH therapy) but remained low in standard treated patients. For the subset of 27 patients examined also at day 8–12, the differences depending on initial CBF level were no longer statistically significant. Among patients with still low CBF at day 4–7, the proportion who had poor short-term outcome was 55% compared to 35% (n.s.) for patients with high CBF.ConclusionsCBF studied in poor-grade SAH patients at large did not show any statistically significant changes over time. Stratifying patients by high or low initial CBF and whether HHH therapy was given revealed an association between low initial CBF and persistent low CBF at day 4–7. These findings may be of clinical relevance in managing SAH patients with low early CBF.

Effect of Electrical Vagus Nerve Stimulation on Cerebral Blood Flow and Neurological Outcome in Asphyxial Cardiac Arrest Model of Rats.

Vagus nerve stimulation (VNS) during post-resuscitation may increase recovery of cerebral blood flow (CBF) and reduce neurological injury. This study was designed to investigate the effect of electrical VNS on neurological outcomes following cardiac arrest (CA). Male Sprague-Dawley rats (n = 48) were subjected to the asphyxial CA model and blindly allocated to the VN isolation (CA + VN isolation) or VNS group (CA + VNS group). Cardiopulmonary resuscitation was initiated 450s after pulseless electrical arrest, and the left cervical vagus nerve was electrically stimulated (0.05mA, 1Hz) for 3h in the CA + VNS group. The neurological deficit score (NDS) and overall performance category (OPC) were assessed at 24h after resuscitation, and histological injury of the hippocampus was evaluated. Independent experiments were performed to evaluate the effect of VNS on global cortical CBF after resuscitation using laser speckle Doppler imaging through a thinned skull window from pre-arrest to 6h after resuscitation. The baseline characteristics were not significantly different between the two groups. The NDS was significantly higher, and the OPC was substantially lower in the CA + VNS group (p = 0.022 and p = 0.049, respectively) supported by decrease in histological injury of the hippocampal CA1 region. CBF in the early period of post-return of spontaneous circulation (ROSC) was significantly higher in the CA + VNS group (p < 0.05 at post-ROSC 2h and 4h), and 4-hydroxynonenal was significantly lower in the CA + VNS group (p = 0.026). VNS improved cerebral perfusion and neurological outcomes at 24h after ROSC in an asphyxial CA model of rats.

Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT

BackgroundManagement of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions.Methods Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0–3, 4–7, and 8–12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0–48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients.ResultsTwenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6–33.9) to 38.4 (IQR 27.0–41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time.ConclusionsHHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.

The Correlation between Cerebral Blood Flow Measured by Bedside Xenon-CT and Brain Chemistry Monitored by Microdialysis in the Acute Phase following Subarachnoid Hemorrhage.

Cerebral microdialysis (MD) may be used in patients suffering from subarachnoid hemorrhage (SAH) to detect focal cerebral ischemia. The cerebral MD catheter is usually placed in the right frontal lobe and monitors the area surrounding the catheter. This generates the concern that a fall in cerebral blood flow (CBF) and ischemic events distant to the catheter may not be detected. We aimed to investigate if there is a difference in the association between the MD parameters and CBF measured around the MD catheter compared to global cortical CBF and to CBF in the vascular territories following SAH in the early acute phase. MD catheter was placed in the right frontal lobe of 30 SAH patients, and interstitial glucose, lactate, pyruvate, glycerol, and lactate/pyruvate ratio were measured hourly. CBF measurements were performed during day 0–3 after SAH. Global cortical CBF correlated strongly with CBF around the microdialysis catheter (CBF-MD) (r = 0.911, p ≤ 0.001). This was also the case for the anterior, middle, and posterior vascular territories in the right hemisphere. A significant negative correlation was seen between lactate and CBF-MD (r = −0.468, p = 0.009). The same relationship was observed between lactate and CBF in anterior vascular territory but not in the middle and posterior vascular territories. In conclusion, global CBF 0–3 days after severe SAH correlated strongly with CBF-MD. High lactate level was associated with low global CBF and low regional CBF in the right anterior vascular territory, when the MD catheter was placed in the right frontal lobe.

Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients

Background: Cognitive impairment affects 40%–68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. Methods: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. Results: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale–Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). Conclusion: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Quantitative Lobar Cerebral Blood Flow for Outcome Prediction after Traumatic Brain Injury

The aim of this study was to examine cortical cerebral blood flow (CBF) in patients with traumatic brain injury (TBI) and determine whether lobar cortical CBF is a better predictor of long-term neurological outcome assessed by the Glasgow Outcome Scale (GOS) than global cortical CBF. Ninety-eight patients with TBI had a stable xenon computed tomography scan (Xe/CT-CBF study) performed at various time points after their initial injury. Spearman's correlation coefficients and Kruskall-Wallis' test were used to examine the relationship between patient age, emergency room Glasgow Coma Scale (GCS), Injury Severity Score, prehospital hypotension, prehospital hypoxia, mechanism of injury, type of injury, side of injury, global average CBF, lobar CBF, number of lobes with CBF below normal, and GOS (discharge, 3 and 6 months). Univariate ordinal regression was performed using these same variables and in combination with principle component analysis (PCA) to determine independent variables for multi-variate ordinal regression. Significant correlation between age, GCS, prehospital hypotension, type of injury, global average CBF, lobar CBF, number of lobes below normal CBF, and GOS was found. Individual lobar CBF was highly correlated with global CBF and the number of lobes below normal CBF. PCA found one principle component among these three CBF variables; therefore, average global CBF and number of lobes with CBF below normal were each chosen as independent variables for multiple ordinal regression, which found age, GCS, and prehospital hypotension, global average CBF, and number of lobes below normal CBF significantly associated with GOS. This study found global average CBF and lobar CBF significantly correlated with GOS at follow-up. There was, however, no individual cerebral lobe that was more predictive than any other, which puts into question the value of calculating lobar CBF versus global CBF in predicting GOS.

Brain Neuroimaging in Cannabis Use: A Review

In this study, the authors systematically reviewed structural and functional neuroimaging studies of cannabis use. Structural abnormalities generally have not been identified with chronic use. Regular users demonstrate reciprocal changes in brain activity globally and in cerebellar and frontal regions. Abstinence results in decreases, and administration results in increases correlating with subjective intoxication. Chronic use and cannabis administration result in attenuated brain activity in task-activated regions or activation of compensatory regions. Findings correlate partially with neuropsychological data, but generalization is limited by the lack of use of diagnostic criteria, appropriately paired neuropsychological testing or means to better quantify cannabis use and abstinence.

The role of cerebral blood flow and cerebrovascular reserve capacity in the diagnosis of chronic hydrocephalus--a PET-study on 60 patients.

To investigate the clinical value of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in the management of chronic hydrocephalus. Global cortical CBF and CVR in 60 patients (66 +/- 12 yrs) with chronic hydrocephalus were investigated before, one week (7 d) and 7 months (7 m) after shunting by 15-O-H2O PET (Siemens ECAT 951/31) at rest and after application of acetazolamide (1 g). After 7 months, clinical outcome was assessed according to Stein and Langfitt and patients were classified into responder (n = 31) and non-responder (n = 29). Before Surgery, responder had lower blood flow values compared to non responder (36 +/- 8 vs. 41 +/- 11 ml/100 ml/min; p = 0.04), whereas CVR was not different between outcome groups (33 +/- 10 vs. 41 +/- 8%; p > 0.05). After shunting, CVR in non-responder decreased from 41 +/- 8% to 32 +/- 5% (7 d), whereas in responder significant increases (p < 0.02) to 55 +/- 46% (7 d) and 54 +/- 31% (7 m) were observed. Regarding early individual changes in CVR, the majority (12/18; 66%) of non-responder had marked decreases in CVR-levels (< 30%), whereas clinical responder considerably improved in CVR (> 30%) in half of patients (7/14). Measurement of cerebral blood flow in chronic hydrocephalus might substantially contribute to selection of shunt candidates and neurological sequels may be rather related to early regeneration of the hemodynamic reserve.

PET-studies in idiopathic chronic hydrocephalus before and after shunt-treatment: the role of risk factors for cerebrovascular disease (CVD) on cerebral hemodynamics.

To investigate the impact of cerebrovascular risk factors in idiopathic chronic hydrocephalus concerning cerebral hemodynamics and clinical outcome after shunting. Global cortical cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in 53 patients (67 +/- 11 yrs) were determined by 15-0-water-PET studies before and after administration of acetazolamide (1 g) prior (pre), one week (7 d) and seven months (7 m) after shunting. According to the prevalence of vascular risk factors (American subcommittee on reporting standards for cerebrovascular disease) patients were classified into a "low-risk" (n = 27) and "high-risk" (n = 20) group; patients with a history of stroke (n = 6) were separated. After 7 months, clinical outcome was assessed according to Stein and Langfitt. While CBF in "high-risk" patients prior to surgery was significantly lower in clinical responder compared to non-responder (32 +/- 5 vs. 42 +/- 15 ml/100 ml/min; p < 0.05), CVR was marginal in both outcome groups (< 30%). One week after shunting, CVR in responder of "high-risk" significantly increased (64 +/- 30 vs. 31 +/- 10% pre; p < 0.01). In "low-risk" patients, differences in CVR prior to shunting were found: CVR was lower in clinical responder than in non-responder (36 +/- 11 vs. 47 +/- 22% pre; p > 0.05) and deteriorated in non-responder (29 +/- 15% vs. 47 +/- 22 pre; p < 0.02) one week after shunting. Different peri-operative characteristics in global CVR regarding clinical response after shunting between both "risk-groups" were observed. Pathophysiological mechanisms upon clinical sequels after shunting in idiopathic hydrocephalus may not be unique.

Cerebral blood flow and metabolism in late-life depression and dementia.

Late-life depression (LLD) is characterized by abnormalities in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) for glucose. Unlike younger adults with major depression, global cortical CBF and CMR reductions have been reported in LLD. Patients with LLD are also characterized by topographic abnormalities, most commonly involving selective prefrontal, superior temporal, and anterior parietal cortex. The fate of these abnormalities with response to antidepressant treatment is highly uncertain, and heterogeneous findings have been reported in younger samples with major depression. The limited data in LLD suggest that response to electroconvulsive therapy or antidepressant medications does not involve reversal of baseline abnormalities but rather accentuation of prefrontal deficits. At minimum, these paradoxical findings suggest that abnormalities in CBF and CMR may be persistent in LLD and a trait characteristic. Characteristic profiles of CBF and CMR abnormalities have also been demonstrated in samples with Alzheimer's disease (AD) and other types of dementia. Functional imaging has shown sensitivity to disease severity and progression. Nonetheless, there is limited information regarding the sensitivity and specificity of the functional imaging modalities in the differential diagnosis of dementias. At present, the evidence does not support the use of functional imaging in isolation as a diagnostic tool. Rather, these imaging modalities may be considered as an adjunct to careful clinical assessment, either to improve diagnosis in early cases or to assist in subtyping difficult cases.

Relationship between global and cortical cerebral blood flow in patients with head injuries

OBJECTIVE: The goal of this study was to analyze the use of thermal diffusion-cerebral blood flow (TD-CBF) monitoring as a continuous monitoring method for patients with head injuries in the intensive care unit. METHODS: The TD-CBF probe was placed on normal-appearing frontal or parietal cortex at the time of surgery to treat traumatic intracranial hematomas in 35 patients, and cortical cerebral blood flow (CBF) was monitored for up to 7 days after surgery. We compared TD-CBF values with global CBF values measured by the standard Kety-Schmidt technique, and we compared changes in TD-CBF with changes in jugular venous oxygen saturation observed during intracranial pressure elevations. RESULTS: The average value for the global CBF measurements was 50.5+/-0.9 ml/100 g/min and that for the TD-CBF measurements was 60.5+/-1.4 ml/100 g/min; the average difference was 9.3+/-1.2 ml/100 g/min. The overall slope of the regression between the global CBF and TD-CBF measurements (n = 206) was 0.636 (comparison of observed slope with a slope of 0, P < 0.001). The relationship between the TD-CBF and global CBF values during 546 episodes of increased intracranial pressure was examined by comparing the changes in TD-CBF with the changes in jugular venous oxygen saturation. When the change in TD-CBF was at least 10 ml/100 g/min during an intracranial pressure elevation, the TD-CBF change reflected the change in jugular venous oxygen saturation on 85% of the occasions. CONCLUSION: The TD-CBF method is very convenient because of the continuous and automatic nature of the measurements. Most of the time, a change in TD-CBF indicated a similar change in global CBF. However, the limitations of local measurements of CBF must be kept in mind during therapeutic decision-making.